Sustained effect of SQ-standardized grass allergy immunotherapy tablet on rhinoconjunctivitis quality of life.

BACKGROUND: The prevalence of allergic rhinoconjunctivitis has increased significantly over the past decades with grass pollen being a common trigger. The impact of allergy on patient's quality of life is substantial. AIM: To investigate the sustained effect on quality of life during the grass pollen season 1 year after 3 years of treatment with the SQ-standardized grass allergy immunotherapy tablet (AIT), Graza (Phleum pratense 75,000 SQ-T/2800 BAU; ALK, Denmark). METHODS: The trial was a randomized, parallel-group, double-blind, placebo-controlled trial in adult subjects with a history of moderate-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications. Subjects received 3 years of grass AIT (n = 157) or placebo (n = 126), followed by 1 year of follow-up. Quality of life assessments were based on the standardized rhinoconjunctivitis quality of life questionnaire (RQLQ(S)); completed weekly during the entire grass pollen season. RESULTS: During follow-up, the overall RQLQ(S) score for the entire grass pollen season was significantly improved in the active group (relative difference to placebo: 23%, P = 0.004). The improvement was higher during the peak pollen season (28%, P = 0.001). The treatment effect of grass AIT during the follow-up year and the previous three treatment years was similar. Improvements were found in all seven RQLQ(S) domains. The RQLQ(S) as a function of the weekly average pollen counts showed a clear separation between the treatment groups (P < 0.001). CONCLUSION: In subjects inadequately controlled by symptomatic medications, grass AIT provided sustained and clinically relevant improvements in rhinoconjunctivitis quality of life compared to placebo. The effect increased with increasing grass pollen exposure.

Quality assurance ofallergen-specific immunotherapy during a national outbreak of anaphylaxis: results of a continuous sentinel event surveillance system.

BACKGROUND AND OBJECTIVE: Subcutaneous allergen-specific immunotherapy (SCIT) is an effective treatment for patients with allergic asthma and rhinitis. SCIT may be performed in many different ways and good safety profiles have been published. Other studies, however, have reported high frequencies of severe adverse events (SAEs) but without identifying the causes. After an increase in SCIT-related SAEs in Denmark between 2003 and 2004, strict performance regulations were imposed by the authorities. Because safety data from national databases were not available, we implemented a surveillance system aimed at identifying the causes of SAEs. METHODS: We prospectively registered the number of injections and SAEs during SCIT. A slow up-dosing regimen was used and adherence to international standards was optimized. RESULTS: No SAEs were observed with 28 992 injections. The maximal risk per injection was calculated at < 1.3 per 10 000 injections. DISCUSSION: Our results confirm the good safety profile of SCIT. We applied a sentinel SCIT surveillance system that may offer a means of guaranteeing safety by providing online feedback to all participating clinics when SAEs occur in order to explore their causes by root course analyses performed by all participants. Furthermore, such quality assurance documentation may facilitate wider acceptance of SCIT by health care administrators, clinicians, and patients.

Effect of ketone body infusion on plasma catecholamine and substrate concentrations during acute hypoglycemia in man.

Experimental studies have shown that ketone body infusion inhibits the catecholamine response to hypoglycemia. We have studied six men during insulin-induced hypoglycemia who were concomitantly infused with saline or 3-hydroxybutyrate at dose rates of 4 and 13 mg/kg.min. The mean blood concentrations of 3-hydroxybutyrate increased to about 0.45 and 3 mmol/liter, respectively. The results show that the glucose response to insulin; hypoglycemic symptoms; and the adrenaline, noradrenaline, and cortisol responses to hypoglycemia were not influenced by ketone infusion at any dose rate.

Reproducibility of challenge tests at different times.

Bronchial challenge for determination of bronchial reactivity is widely used in the diagnosis of asthma, the grading of severity, and evaluation of effect of treatment with new antiasthmatic drugs. Allergen challenge is also used for diagnosis of specific IgE-mediated asthma and evaluation of the effect of immunotherapy. A number of factors influence the result of the challenge test including the selection of patients, criteria for carrying out the challenge test, a number of technical factors concerning the challenge, the dosing schedule, pulmonary function tests carried out and analysis of the data. All these factors have to be taken into consideration before reproducible challenge tests can be performed. Detailed description of the equipment and procedures used and inclusion criteria for the patients should be included in all publications concerning challenge tests in order to be able to compare results from different laboratories. Each clinic or laboratory needs to perform reproducibility studies on bronchial challenge testing procedures and equipment used in their clinic.

Office spirometry: temperature conversion of volumes measured by the Vitalograph-R bellows spirometer is not necessary.

The aim of the present study was to investigate the relevance of BTPS (gas at body temperature, atmospheric pressure and saturated with water vapour) conversion of volumes measured with the Vitalograph bellows spirometer. The Vitalograph bellows were tested against a MicroMedical turbine spirometer in extreme temperatures (0-37 degrees C) using a biological control to deliver expired gas at BTPS. Before testing, it was shown that the accuracy of the DairyCard turbine was stable in the relevant temperature range. In a clinical trial six patients with emphysema performed home spirometry b.i.d for 1 month using both the Vitalograph and the turbine. Both the DairyCard and the Vitalograph showed stable accuracy at extreme temperatures when results were reported without any BTPS conversion. These findings were supported by the clinical trial but the conclusions from the clinical setting were weakened by the surprising fact that domiciliary temperatures showed almost no variation. We conclude that the Vitalograph bellows, during dynamic spirometry, measures expired volume at conditions closer to BTPS (than to ATPS) gas at ambient temperature, atmospheric pressure and saturated with water vapour). The use of the BTPS correction based on ambient temperature seems unjustified at office temperatures close to 23 degrees C and at extreme temperatures the conversion of volume will introduce significant over or underestimation.

Secular trends of allergic asthma in Danish adults. The Copenhagen Allergy Study.

Numerous studies have reported increases in asthma prevalence among children world-wide. Less is known about similar trends in adults. We aimed to investigate whether the prevalence of allergic asthma symptoms had increased in an adult general population. Two cross-sectional surveys using identical methods were carried out in 1989 and 1998. A one-page questionnaire on respiratory symptoms was mailed to random samples of 15-41-year-olds living in Copenhagen. The response rates were 86.6% (3624/4185) and 78.8% (2402/3048) in 1989 and 1998, respectively. The questionnaire was validated with specific immunoglobilin E (IgE) positivity as the reference in a random sample of responders in connection with both surveys. We found a significantly increased prevalence of subjects who reported shortness of breath on exposure to pollens (6.6% 0 s. 10.3%, odds ratio 1.61, 95% CI 1.34-1.95), furry animals (5.4% vs. 7.6%, odds ratio 1.45, 95% CI 1.17-1.79), and house dust (7.8% vs. 10.2%, odds ratio 1.35, 95% CI 1.12-1.61). The validation of these symptoms showed that the positive predictive values were reasonably stable over time, which may support that a true increase in allergic asthma has occurred. In conclusion, the prevalence of allergic asthma symptoms increased significantly in this adult general population over a 9-year period.

Patient-administered sequential spirometry in healthy volunteers and patients with alpha 1-antitrypsin deficiency.

The launching of cheap, pocket-sized spirometers, with data storage capability, has made patient-administered sequential spirometry (PASS) an attractive method of monitoring ventilatory capacity. At present, little information is available on the quality of PASS, compared to laboratory spirometry. The aim of this study was to investigate whether patients could perform PASS without loss of reliability and reproducibility as compared with traditional laboratory spirometry. Ten healthy volunteers performed spirometry for 1 month and 10 emphysematous patients with alpha 1-antitrypsin deficiency (type PiZ) performed spirometry twice daily for up to 2 yr. To fulfil Good Clinical Practice criteria on full data documentation, a traditional direct recording spirometer, the Vitalograph R-model, was used. A decompression device was used for calibration and a 3.8% annual drift in volume registration was noted. This drift was largest for the first year. After training, all patients were able to perform unsupervised spirometry, producing technically correct forced expiratory curves. Reproducibility of FEV1 and FVC obtained by PASS was found to be as good as for laboratory spirometry. After adjustment for the diurnal variation, the residual variation of FEV1 was 2.5% (range 1.6-4.2%) for healthy volunteers and 5.6% (range 4.2-7.7%) for emphysematous patients. Forced vital capacity showed the same pattern. In conclusion, PASS is possible in highly motivated individuals without loss of reliability and reproducibility when compared to laboratory spirometry.

Multidisciplinary intensive treatment for chronic low back pain: a randomized, prospective study.

BACKGROUND: Americans with low back pain have been helped to return to work by multidisciplinary intensive treatment programs. Whether this treatment method will succeed in countries with a more generous social welfare system, where the incentive to return to work might be less, is not proven. OBJECTIVES: To evaluate a Danish program of functional restoration combined with behavioral support. METHODS: Patients who had experienced at least 6 months of disabling low back pain were randomly assigned to either a 3-week intensive treatment program (n = 55) or an untreated control group (n = 51). RESULTS: Of the 106 patients randomized, 94 (89%) returned for a 4-month follow-up visit. At that time, 29 (64%) of the 45 treated patients were able to work, compared with 14 of 49 (29%) in the control group. The treated patients had used fewer days of sick leave (P < .02), had contacted health care. professionals fewer times (P < .001), and had lower pain and disability scores. CONCLUSIONS: Although such programs are expensive, they can reduce pension expenditures, sick leave days, health care contacts, and pain.

Comparison between different techniques for measuring nasal patency in a group of unselected patients.

Many techniques for measuring nasal patency have been developed in search for a reliable, easily performed and reproducible method. Rhinomanometry is easily performed in the clinic but daily records of nasal blocking cannot be obtained. In this study we examined the correlation between posterior rhinomanometry (PR), nasal peak flow (nPF), the ratio nasal patency index (NPI), and the opening interrupter method (Rtn) for measuring nasal patency. Twenty-eight subjects with no symptoms of rhinitis and 20 patients with diagnosed rhinitis were investigated. A significant (p less than 0.05) correlation was found between PR and nPF after stratification according to the diagnosis of rhinitis and between nPF, PR, and height. All other correlations tested proved non-significant. We conclude that PR is the method which ought to be used in the hospital, but nPF is an easy way to measure nasal patency and might even be used by the patient at home.

[High dose inhaled steroids in the treatment of bronchial asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial reactivity and adrenocortical function]. / Højdosis inhalerede steroider i behandlingen af asthma bronchiale. En sammenligning af effekten af budesonid og beklometason-dipropionat på lungefunktion, symptomer, bronkial reaktivitet og binyrebarkfunktion.

The effects of high-dose inhaled budesonide (800 micrograms twice daily) and those of inhaled beclomethasone dipropionate (750 micrograms twice daily) were compared with respect to lung function, symptoms, bronchial reactivity and adrenocortical function in a doubleblind, double-dummy cross-over study. The subjects were 40 adult patients suffering from either allergic or non-allergic asthma. The asthma was categorized as moderate to severe, and the asthma was insufficiently controlled on inhalational steroids given in doses of 300 to 500 micrograms daily. After a two week "run-in" period the patients were randomized to six weeks treatment with either budesonide or beclomethasone dipropionate, followed by six weeks treatment with the opposite drug. Both inhaled budesonide and inhaled beclomethasone dipropionate were able to improve objective measures of lung function and bronchial sensitivity to histamine. Neither drug affected adrenocortical function, and no serious side-effects were noted during the trial. It is concluded that budesonide and beclomethasone dipropionate are safe and effective drugs for the treatment of asthma in adults. The substances are equally effective taken microgram for microgram.

Screening for allergic respiratory disease in the general population with the ADVIA Centaur Allergy Screen Assay.

BACKGROUND: In patients in whom the clinical indication for immunoglobulin E (IgE)-mediated allergic respiratory disease is weak, a single qualitative multiallergen-screening assay for IgE antibody to multiple allergen specificities may support the absence of IgE-mediated allergic respiratory disease. The aim was to investigate the diagnostic efficacy of a new multiallergen-screening assay in relation to skin prick test (SPT) reactivity and objective diagnoses of allergic respiratory disease in a general population setting. METHODS: A total of 709 participants in a population-based study were examined by questionnaire and SPT. Serum was analysed by using a multiallergen-screening assay: the ADVIA Centaur Allergy Screen (AS) assay. The dichotomized result of the AS assay was compared with SPT reactivity, specific IgE positivity, and a clinical diagnosis of allergic rhinitis or allergic asthma defined by the presence of relevant symptoms and positive SPTs. RESULTS: Sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of the AS against SPT reactivity were 86%, 96%, 94%, and 89%, respectively. A negative AS assay test was able to exclude allergic rhinitis and allergic asthma with a probability of more than 96% and 98% (NPV), respectively. The AS assay was able to identify more than 92% and 92% (sensitivity) of cases of allergic rhinitis and allergic asthma, respectively. CONCLUSIONS: The AS assay proved to be a valid measure of allergic respiratory disease and may be used as a screening tool to rule out allergic respiratory disease, and as an objective measure of allergic respiratory disease in epidemiological studies.

Mucosal symptoms elicited by fragrance products in a population-based sample in relation to atopy and bronchial hyper-reactivity.

BACKGROUND: Exposure to perfume and fragrance products may, in some individuals, cause symptoms from the eyes and airways. The localization, character and risk factors of such symptoms in the general population are unknown. OBJECTIVE: To investigate both the localization and character of symptoms from the eyes and airways elicited by fragrance products, and the associations between such symptoms and skin prick test reactivity (atopy), methacholine bronchial hyper-reactivity (BHR), allergic rhinitis and asthma. METHODS: A questionnaire on mucosal symptoms elicited by fragrance products was posted to 1189 persons who had participated in a Danish population-based study of allergic diseases in 1997/1998. The study included measurement of BHR, atopy, forced expiratory volume in 1 s (FEV1), and serum eosinophilic cationic protein (serum ECP). RESULTS: The response rate was 79.6%. Symptoms from the eyes or airways elicited by fragrance products were reported by 42%. BHR (adjusted odds ratio 2.3, 95% confidence interval 1.5-3.5) was independently associated with symptoms from the eyes and airways elicited by fragrance products. There were no significant associations between these symptoms and atopy, FEV1 or serum ECP. CONCLUSIONS: Mucosal symptoms from the eyes and airways were common in this population. BHR was a significant and independent predictor of these symptoms. The lack of association with atopy suggested that IgE-mediated allergic mechanisms do not play a major role in the development of these symptoms.