Basophil allergen threshold sensitivity, CD-sens, is a measure of allergen sensitivity in asthma.

BACKGROUND: Allergic asthma is IgE-mediated and the IgE-sensitisation is usually demonstrated by skin prick tests (SPT) and IgE antibody determinations in serum. The SPT and IgE-antibody values do not directly predict if the allergy clinically contributes to the asthma. There is therefore a need for new objective tests that may indicate the clinical importance of an IgE-sensitisation. OBJECTIVE: To evaluate basophil allergen threshold sensitivity (CD-sens) as a measure of allergen sensitivity in allergic asthma. METHODS: Twenty-six subjects with stable, intermittent allergic asthma were tested with SPT and spirometry, and methacholine and allergen inhalation challenges to determine methacholine PD(20) (provocative dose causing a 20% drop in forced expiratory volume in 1 s) and allergen PD(20) . The results were compared with CD-sens and serological parameters, i.e. IgE- and IgG4 antibodies to the relevant allergens. RESULTS: A significant correlation was found between CD-sens and allergen PD(20) (P = 0.01; r = 0.49; n = 26) as well as between CD-sens and the ratio of allergen PD(20) to methacholine PD(20) (P = 0.007; r = 0.52; n = 26). In patients with a moderate to low degree of bronchial hyperresponsiveness there was an excellent correlation (P = 0.0001; r = 0.88, n = 13) between CD-sens and allergen sensitivity. No relation to either allergen PD(20) or the ratio was found for basophil allergen reactivity measured as CD63 up-regulation at high concentrations of the respective allergen. CONCLUSIONS AND CLINICAL RELEVANCE: CD-sens was found to be an objective marker of airway allergen sensitivity in stable allergic asthmatics, that may be used to predict airway responsiveness when bronchial challenge tests cannot be performed.

Functional endoscopic sinus surgery improved asthma symptoms as well as PEFR and olfaction in patients with nasal polyposis.

BACKGROUND: Nasal polyposis is a disease known to be associated with asthma. The management is anti-inflammatory, with topical and oral corticosteroids as the first-line treatment. The effect of surgical treatment on lower airway inflammation has not been sufficiently studied. AIM: The aim of this study is to investigate the effects of functional endoscopic sinus surgery (FESS) as well as fluticasone proprionate nasal drops (FPND) 400 microg b.i.d. on nasal and lower airway parameters in asthmatics with nasal polyposis. METHODS: This was a prospective 21-week study of 68 patients with asthma and nasal polyposis, on the benefits of FESS on nasal '(butanol test, subjective olfaction, peak nasal inspiratory flow, congestion, rhinorrhoea, and polyp score)', and on the lower airway parameters (dyspnea, cough, mean daily peak expiratory flow rate (PEFR), and lung function tests). It also included a randomized, double-blind, placebo-controlled 14 weeks phase on FPND. RESULTS: Functional endoscopic sinus surgery significantly improved mean asthma symptom scores and daily PEFR and all nasal parameters including subjective and objective olfaction tests. This is the first study that shows the benefits of FESS on butanol tests in patients with nasal polyposis. We found no significant difference between topical treatment with FPND or placebo in the nasal or lower airway variables. CONCLUSION: Functional endoscopic sinus surgery improved nasal and asthma symptoms in patients with nasal polyposis. Functional endoscopic sinus surgery could be considered early in the natural course of nasal polyposis with concomitant asthma, as well as a second-line treatment in nasal polyposis patients with a reduced sense of smell. The potential benefits of FPND 400 microg b.i.d. were probably overshadowed by FESS.

Effect of formoterol with or without budesonide in repeated low-dose allergen challenge.

The use of combination therapy in mild asthma is debated. The current authors evaluated the effects of formoterol alone and a formoterol/budesonide combination inhaler on asthma deterioration induced by repeated low-dose allergen exposure. In total, 15 subjects with intermittent allergic asthma inhaled low doses of allergen on seven consecutive weekdays in a three-period, crossover, double-blind, double-dummy comparison between formoterol 4.5 microg Turbuhaler, budesonide 160 microg/formoterol 4.5 microg Turbuhaler and placebo, each taken as two puffs 30 min after allergen dosing. The outcome variables were: provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD(20)), exhaled nitric oxide fraction (F(eNO)), sputum eosinophils and prostaglandin D(2), and diary card recordings of symptoms (on a scale of 0-10), short-acting beta(2)-agonist use and evening forced expiratory volume in one second (FEV(1)). With placebo treatment, allergen exposure caused significant increases in airway hyperresponsiveness (geometric mean (coefficient of variation) PD(20): 397 (98) microg before versus 168 (82) microg after), F(eNO) (mean+/-sd 46+/-31 ppb before versus 73+/-46 ppb after) and asthma symptom score (mean+/-sd 0.39+/-0.55 before versus 0.68+/-0.67 after). Budesonide/formoterol abolished these changes and significantly improved baseline FEV(1). Formoterol alone, while providing symptom relief, was no better than placebo in protecting against the allergen-induced increase in airway inflammation. Signs of deteriorating asthma, provoked by low-dose allergen, are prevented by short-term use of budesonide/formoterol but not by temporary use of formoterol alone.

Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma.

BACKGROUND: A diagnosis of aspirin-intolerant asthma requires aspirin provocation in specialist clinics. Urinary leukotriene E(4) (LTE(4)) is increased in aspirin-intolerant asthma. A study was undertaken to investigate new biomarkers of aspirin intolerance by comparing basal levels of cysteinyl-leukotrienes (CysLTs) and leukotriene B(4) (LTB(4)) in saliva, sputum and ex vivo stimulated blood in subjects with aspirin-intolerant and aspirin-tolerant asthma. The effects of aspirin- and allergen-induced bronchoconstriction on leukotriene levels in saliva and ex vivo stimulated blood were also compared with the effects of the provocations on urinary mediators. METHODS: Induced sputum, saliva, urine and blood were obtained at baseline from 21 subjects with asthma. At a separate visit, 11 subjects showed a positive response to lysine-aspirin inhalation and 10 were aspirin tolerant. Saliva, blood and urine were also collected on the provocation day. Analyses of CysLTs and LTB(4) and the prostaglandin D(2) metabolite 9alpha,11beta-prostaglandin F(2) were performed and the fraction of exhaled nitric oxide was measured. RESULTS: Subjects with aspirin-intolerant asthma had higher exhaled nitric oxide levels and higher baseline levels of CysLTs in saliva, sputum, blood ex vivo and urine than subjects with aspirin-tolerant asthma. There were no differences in LTB(4) levels between the groups. Levels of urinary LTE(4) and 9alpha,11beta-prostaglandin F(2) increased after aspirin provocation whereas leukotriene levels in saliva and ex vivo stimulated blood did not increase. CONCLUSION: These findings support a global and specific increase in CysLT production in aspirin-intolerant asthma. Measurement of CysLTs in saliva has the potential to be a new and convenient non-invasive biomarker of aspirin-intolerant asthma.

Eosinophil activity reflects clinical status in patients with asthma before and during a prednisolone course.

BACKGROUND: Both overtreating and undertreating asthma can be harmful, either because of side effects or development of uncontrolled asthma. As the eosinophil granulocyte is of importance in asthma, it is logical to study this cell in the search for a marker for the right level of treatment. OBJECTIVE: To study the changes in eosinophil activity and the correlation to clinical status in asthmatic patients who have deteriorated and during prednisolone treatment. METHODS: Nine patients were studied on two occasions: with exacerbation (visit 1) and during prednisolone treatment (visit 2). Clinical evaluation was performed as well as analysis of percentage of eosinophils, eosinophilic cationic protein (S-ECP) in serum and expression of intracellular ECP, measured by cell flow cytometry using a monoclonal antibody (EG2) against the activated form of ECP. RESULTS: Visit 1: four patients had eosinophils above normal, mean 6.5%, range 1.5 to 13.8. S-ECP was measured in seven patients of whom five had values above normal (16 micrograms/L), mean 29.5, range 1.5 to 13.8. Intracellular expression of ECP was above normal (mean 26.7 +/- 10.8) in seven out of nine (mean 48.1, range 28.8 to 69.6). Visit 2: all patients improved and all eosinophil parameters decreased. The eosinophil concentration fell to a mean of 3.0%, range 1.0 to 6.6, S-ECP to a mean of 10.5 micrograms/L, range 3.2 to 17 and intracellular expression of ECP to a mean of 33.4, range 19.4 to 40.9. CONCLUSIONS: Reduction in eosinophil activity followed improvement in clinical condition. Measuring intracellular expression of ECP may be of value in addition to eosinophil count and S-ECP in monitoring asthma.

Spirometry and ventilation-perfusion inequality in patients with mild allergic asthma before and during the pollen season.

Several studies on asthma have shown a low correlation between gas exchange and spirometry, especially after treatment with bronchodilators. The aim of the present study was therefore to examine both spirometry results and gas exchange during a pollen-free period and at the end of the pollen season in patients with mild and well-controlled allergic asthma. Pulmonary gas exchange was studied using a modified form of the multiple inert gas elimination technique. Lung volumes and forced expiratory flows were measured by common spirometry. During the non-pollen season, spirometry and forced expiratory flows were within the reference values in all but one patient, who had decreased indices for airway flow. Three other patients showed signs of minor gas exchange impairment. During the pollen season, FRC was slightly increased (P < 0.05) and MEF50 was slightly decreased (P < 0.05) for the group. Two patients had an increased index for gas exchange impairment (log SDQ was 0.64 and 0.59) and four patients had borderline log SDQ (0.50 to 0.56). However, the mean log SDQ was not increased in the pollen season. The results show that, both in the pollen season and in the pollen-free season, low degrees of gas exchange impairment could be present in pollen allergic asthmatic patients despite normal spirometry. The low degree of gas exchange impairment in some patients indicates the presence of airway inflammation with oedema and/or secretion. However, high degrees of ventilation-perfusion inequality were not observed in these patients where air flow rates were mainly normal.

Dose potency relationship of terbutaline inhaled via Turbuhaler or via a pressurized metered dose inhaler.

OBJECTIVE: The relative dose potency of cumulative doses of terbutaline sulfate inhaled via Turbuhaler and via a pressurized metered dose inhaler was estimated with respect to lung efficacy and systemic effect. METHODS: The study was an open, crossover, randomized, multicenter study including 31 adult patients with asthma [forced expiratory volume in one second (FEV1), 65% of predicted]. The patients inhaled terbutaline doses of 0.125, 0.125, 0.25, 0.5, 1.0, and 2.0 mg (a total of 4 mg) at 30-minute intervals. Lung function [FEV1, forced vital capacity (FVC), forced expiratory flow at 75% of FVC (FEF75%), and peak expiratory flow (PEF)], and systemic effect variables (serum potassium, tremor, pulse, blood pressure) were monitored prior to the first inhalation and 15 to 25 minutes after each inhaled dose. RESULTS: The mean relative dose potency of terbutaline inhaled via Turbuhaler compared with pressurized metered dose inhaler was 1.5 (95% confidence interval: 1.2 to 1.8) with respect to FEV1 and serum potassium, respectively. The corresponding relative dose potencies for PEF, FVC, and FEF75% were 1.0, 1.2, and 1.6, respectively, with no statistically significant difference between the two devices. No differences between the devices were evident with regard to blood pressure and pulse. CONCLUSION: The results suggest that Turbuhaler is more efficient in the delivery of inhaled terbutaline to the lungs compared with the conventional pressurized metered dose inhaler.

Lability in complement receptor mobilization of granulocytes in patients with bronchial hyperreactivity.

The recruitment of activated granulocytes to bronchial mucosa seems to be involved in the prolonged inflammatory response observed in asthma and probably associated with bronchial hyperresponsiveness. We studied the patients with bronchial hyperresponsiveness with respect to the expression of complement receptor type 1 (CR1), its variability and readiness to become mobilized on peripheral granulocytes from patients with bronchial hyperresponsiveness. CR1 expression and its hourly variation was significantly (P less than 0.02, P less than 0.01 respectively) higher in the patient group compared with the control group. In addition the ability to mobilize CR1 spontaneously at +37 degrees C correlated to the variation of CR1 expression that occurred during a 4 hr period. These findings indicate that granulocytes from patients with bronchial hyperresponsiveness have a higher degree of variation in CR1 expression that correlates to their ability to mobilize CR1 and may reflect a more pronounced lability.

Changes of stapedius reflex and hearing threshold in patients receiving high-dose cisplatin treatment.

The value of stapedius reflex (SR) measurement in the clinical management of the ototoxic side-effect of cisplatin was examined in 24 patients who had received a dose of 100-120 mg/m2. The main finding was a frequent but inconsistent deterioration of the SR threshold (SRT) at 3 and/or 4 kHz, usually with a moderate rise of the hearing threshold (HT) in the frequency range 3-8 kHz. A hearing loss exceeding 60 dB HL is detected with high probability as an SRT deterioration. None of the patients showed any influence on the SRT before the HT rise could be detected. The SR test cannot replace pure-tone audiometry for the identification of cisplatin ototoxicity. The pathological SR results observed in this study indicated a cochlear lesion. It was not possible to identify those patients most susceptible to ototoxic changes from the pretreatment results of the SR test.

Effect of disodium cromoglycate on neutrophil movement and intracellular calcium mobilization.

Disodium cromoglycate (DSCG) is a widely used drug in the treatment of allergy and asthma. Although its mode of action is not completely understood, it appears to prevent activation and release of mediators from mast cells. Neutrophils may also play a prominent role in clinical asthma and in other diseases of the airways. We have therefore studied the effect of DSCG on the activation of neutrophils from healthy adults. DSCG in concentrations of 1, 10, and 50 micrograms/ml significantly inhibited chemotaxis to zymosan-activated serum or formyl-methionyl-leucyl-phenylalanine. When leukotriene B4 was used as the chemoattractant, no inhibition was found. Incubation of the cells with the drug for 30 minutes elicited the most pronounced inhibition. Since calcium is a key factor in the activation of cells, we used the calcium-specific probe Quin-2 to examine free levels of this cation after chemotactic-factor stimulation. Treatment of neutrophils with DSCG significantly reduced intracellular free calcium levels induced by zymosan-activated serum but not leukotriene B4. Thus, it appears that DSCG may function not only to stabilize mast cells in allergy and clinical asthma but also may interfere with neutrophil activation and movement into the airways.

Allergy to weeping fig--a new occupational disease.

During the last decade green plants have become more common in interior decoration. There are companies specializing in the leasing of green plants to public buildings and offices. Weeping fig is one of the most popular green plants. Dust and dry components of the plant are usually removed by vigorous shaking. In this way the allergen becomes airborne. During a few months we have seen several plant keepers who have developed airway allergy to weeping fig. Two of them have been thoroughly investigated. Both are atopics. Extracts were made from leaves and branches and both patients had positive skin prick tests and RAST. The risk of sensitization in plant keepers who work with weeping fig is probably considerable.

A comparison of sustained-release terbutaline with ordinary salbutamol in bronchial asthma.

The effects of a sustained-release preparation of terbutaline, depot tablets, 7.5 mg 2 times/day were compared with ordinary salbutamol tablets 4 mg 3 times/day. The study, performed for 2 weeks, one week on each treatment, was double-blind, double-dummy, crossover with randomized allocation of the drugs. Twenty-five patients with chronic bronchial asthma completed the trial. The morning Peak-Flow was higher during the period on the depot tablets compared to that on the ordinary tablets (p less than 0.05). No differences were found in side effects.