Prevalence, classification and perception of allergic and nonallergic rhinitis in Belgium.

BACKGROUND: Allergic rhinitis (AR) and noninfectious, nonallergic rhinitis (NINA) are common disorders, which may prompt patients to seek medical help. METHODS: We performed a survey in a representative sample of the Belgian population (n=4959) with an overall prevalence of self-declared recent rhinitis symptoms of 39.3%. Detailed information on patients having experienced nasal symptoms over the past year was then obtained from a random sample of respondents (n=743). RESULTS: The adjusted prevalence was 29.8% for AR and 9.6% for NINA, respectively. According to the ARIA classification, there was significantly more 'persistent' symptomatology in the AR group (40.8%) than in NINA (23.5%) (P<0.001), and more 'moderate/severe' symptom intensity in AR (75.4%) than in NINA (53.1%) (P<0.001). Allergic rhinitis patients suffered from a greater number of symptoms than NINA patients (P<0.001). Asthma, skin and food allergy as co-morbidities were all found to be significantly more prevalent in the AR vs the NINA group (P<0.05 for all). The percentage of consulting patients (total: 66.8%), who subjectively perceived their rhinitis as moderate/severe, was 94.0%, whereas 75.6% of these patients were classified accordingly based on ARIA criteria. CONCLUSIONS: We found a high prevalence of self-declared rhinitis symptoms in the Belgian population, AR being about three times more prevalent than NINA. In addition, AR patients suffered from a greater number of symptoms and displayed a more 'persistent' and 'moderate-severe' ARIA profile than NINA. About 75% of patients seeking medical help suffer from 'moderate to severe' forms of rhinitis.

Effect of inhaled fluticasone on bronchial responsiveness to neurokinin A in asthma.

Neurokinin (NK) A causes airway narrowing in patients with asthma through direct and indirect mechanisms. The effects of the inhaled glucocorticosteroid fluticasone propionate (FP) on the bronchial responsiveness to NKA and methacholine were studied. Patients (n=11) with mild asthma participated in a randomized, double-blind, placebo-controlled crossover trial. FP (500 microg b.i.d.) or matched placebo was administered via Diskhaler for 14 days. Bronchial challenges were performed on days 1 and 13 (methacholine) and 0 and 14 (NKA) for each treatment period. At the active treatment period, the mean log2 provocative concentration causing a 20% fall in the forced expiratory volume in one second (PC20)+/-SEM for NKA was -12.72+/-0.63 at the beginning and -9.77+/-0.49 at the end of the period (p<0.0001), while under placebo, it was -12.16+/-0.82 and -12.19+/-0.51 respectively (NS). At the active treatment period, the mean log2 PC20 for methacholine was -5.25+/-0.40 at the beginning and -4.22+/-0.31 at the end of the period (p=0.012), while under placebo, it was -5.47+/-0.47 and -5.24+/-0.42 respectively (NS). The reduction in response to NKA was significantly larger than that for methacholine. A 2-week course of an inhaled steroid reduces bronchial responsiveness to neurokinin A, an effect more pronounced than the reduction in bronchial responsiveness to methacholine.

Lung deposition and protective effect of terbutaline delivered from pressurized metered-dose inhalers and the Turbuhaler in asthmatic individuals.

We investigated the relationship between pulmonary deposition of terbutaline and bronchoprotection against methacholine and histamine with the Turbuhaler (AstraZeneca, Lund, Sweden) and a pressurized metered dose inhaler (pMDI) in 13 asthmatic patients. The study was done with a randomized, double blind, double dummy, and crossover design. On different days, the provocative concentration of histamine causing a 20% decrease in FEV(1) (PC(20) histamine) and PC(20) methacholine were determined before and at 1.5, 3, and 6 h after inhalation of 0.25 or 0.5 mg of terbutaline sulfate. The Turbuhaler delivered significantly more drug than did the pMDI (% of the nominal metered dose and 95% confidence interval): 20.8% (16.4 to 26.6%) and 16.9% (13.2 to 21.7%) versus 4.8% (3.8 to 6.1%) and 7.4% (5.8 to 9.5%), respectively. Average protection against histamine over 6 h was 0.66 (95% CI: 0.45 to 0.87) doubling concentrations (DC) after inhalation of 0.25 mg and 1.08 (95% CI: 0.87 to 1.29) DC after 0.5 mg terbutaline via pMDI, and 1.07 (95% CI: 0.87 to 1.29) DC after 0.25 mg and 1.24 (95% CI: 1.03 to 1.45) DC after 0.50 mg via Turbuhaler. Protection against methacholine was also dose- and device-dependent. The dose needed to obtain the same pulmonary deposition with the pMDI was 3.14 times greater than with the Turbuhaler, and that needed for the same protective effect was 2.1 and 3.2 times greater for histamine and methacholine, respectively. We conclude that pulmonary deposition of terbutaline was predictive of the clinical response.

Indirect bronchial hyperresponsiveness in asthma: mechanisms, pharmacology and implications for clinical research.

Bronchial hyperresponsiveness (BHR), an abnormal increase in airflow limitation following the exposure to a stimulus, is an important pathophysiological characteristic of bronchial asthma. Because of heterogeneity of the airway response to different stimuli, the latter have been divided into direct and indirect stimuli. Direct stimuli cause airflow limitation by a direct action on the effector cells involved in the airflow limitation, while indirect stimuli exert their action essentially on inflammatory and neuronal cells that act as an intermediary between the stimulus and the effector cells. This manuscript reviews the clinical and experimental studies on the mechanisms involved in indirect BHR in patients with asthma. Pharmacological stimuli (adenosine, tachykinins, bradykinin, sodium metabisulphite/sulphur dioxide, and propranolol) as well as physical stimuli (exercise, nonisotonic aerosols, and isocapnic hyperventilation) are discussed. The results of the different direct and indirect bronchial challenge tests are only weakly correlated and are therefore not mutually interchangeable. Limited available data (studies on the effects of allergen avoidance and inhaled corticosteroids) suggest that indirectly acting bronchial stimuli (especially adenosine) might better reflect the degree of airway inflammation than directly acting stimuli. It remains to be established whether monitoring of indirect BHR as a surrogate marker of inflammation (in addition to symptoms and lung function) is of clinical relevance to the long-term management of asthmatic patients. This seems to be the case for the direct stimulus methacholine. More work needs to be performed to find out whether, indirect stimuli are more suitable in asthma monitoring than direct ones. Recommendations on the application of indirect challenges in clinical practice and research will shortly be available from the European Respiratory Society Task Force.

Systemic effects of inhaled fluticasone propionate and budesonide in adult patients with asthma.

We assessed the systemic effects of budesonide (BUD) and fluticasone propionate (FP) in 23 patients with asthma, using a double-blind, placebo-controlled, double-dummy, and cross-over design. The following five treatments were given in a randomized order for 1 wk with a washout period in between of 2 wk: (1) placebo; (2) FP, 200 micrograms twice a day, inhaled from a Diskhaler; (3) FP, 1,000 micrograms twice a day, inhaled from a Diskhaler; (4) BUD, 200 micrograms twice a day, inhaled from a Turbuhaler; and (5) BUD, 800 micrograms twice a day, inhaled from a Turbuhaler. The primary variable was the area under the curve of serum cortisol versus time (AUC0-20), derived from serum samples taken every 2 h over a 20-h period following the last evening dose at 10:00 P.M. The lower doses of BUD and FLU did not cause any adrenal suppression. Compared with placebo, however, FP (1, 000 micrograms, twice daily and BUD (800 micrograms, twice daily) decreased the AUC0-20 by 34 and 16%, respectively. Fluticasone (1,000 micrograms, twice daily) was more suppressive than BUD (800 micrograms, twice daily) (p = 0.0006). The FEV1, measured the morning after the last inhalation, was significantly higher after the active treatments, compared with placebo (p < 0.02), but did not differ between all active treatments. We conclude that high doses of BUD and FP (in particular the latter), inhaled via their respective dry powder inhalers for 1 wk, result in a measurable systemic activity in patients with asthma.

The effect of the NK2 tachykinin receptor antagonist SR 48968 (saredutant) on neurokinin A-induced bronchoconstriction in asthmatics.

Inhalation of neurokinin (NK) A causes bronchoconstriction in patients with asthma. The NKA-induced bronchoconstriction in isolated human airways is mediated via the NK2 receptor and inhibited by SR 48968, a potent and specific nonpeptide tachykinin NK2 receptor antagonist. In the present study, the effect of orally administered SR 48968 on NKA-induced bronchoconstriction was examined in 12 mild asthmatics. On the screening day and during the study periods, increasing concentrations of NKA (3.3 x 10(-9) to 1.0 x 10(-6) mol x mL(-1)) were inhaled, until the forced expiratory volume in one second (FEV1) and specific airway conductance (sGaw) decreased by at least 20 and 50%, respectively. During the study periods, 100 mg SR 48968 or matched placebo was ingested in a double-blind, randomized, crossover fashion and NKA provocation was performed at 1.5 and 24 h after dosing. At 1.5 h, the mean (SEM) log10 provocative concentration of NKA causing a 20% fall in FEV1 (PC20 FEV1) was -6.25 (0.20) after SR 48968 and -6.75 (0.17) after placebo (p=0.05); the mean log10 provocative concentration of NKA causing a 35% fall in sGaw (PC35 sGaw) was -7.02 (0.28) after SR 48968 and -7.64 (0.19) after placebo (p=0.05). At 24 h, the mean log10 PC20 FEV1 was -6.21 (0.17) after SR 48968 and -6.65 (0.11) after placebo (p=0.05); the mean log10 PC35 sGaw was -6.85 (0.23) after SR 48968 and -7.17 (0.15) after placebo (nonsignificant). As PC20 FEV1 and/or PC35 sGaw were not reached in up to 4 patients per SR 48968 group, the differences between SR 48968 and placebo were underestimated. In conclusion, oral treatment with 100 mg SR 48968 caused a significant inhibition of neurokinin A-induced bronchoconstriction in asthmatics. This finding constitutes the first evidence of inhibition of sensory neuropeptide-induced bronchoconstriction by a selective tachykinin receptor antagonist in humans.

The effect of ABT-761, a novel 5-lipoxygenase inhibitor, on exercise- and adenosine-induced bronchoconstriction in asthmatic subjects.

Leukotrienes have been implicated in the bronchoconstriction caused by indirect stimuli. In the present study we examined the effect of oral ABT-761, a novel 5-lipoxygenase (5-LO) inhibitor, on exercise- and adenosine (AMP)-induced bronchoconstriction in nine asthmatics. At the four 1-d, single-dose treatment periods, ABT-761 (200 mg) or placebo (P) was ingested 5 h before challenge in a double-blind, crossover fashion. At study periods 1 and 2 the subjects performed an exercise challenge and at study periods 3 and 4 an AMP challenge. Pretreatment with ABT-761 caused a significant inhibition of the maximal percentage fall of FEV1 from baseline (p = 0.037) and a reduction of the percentage fall in FEV1 (area under the curve, AUC) of 61.4 +/- 14.1% (mean +/- SEM) after exercise challenge (p = 0.021). Although pretreatment with ABT-761 did not significantly inhibit the maximal fall of FEV1 after AMP challenge (p = 0.134), the overall bronchoconstriction was significantly inhibited, the AUC being reduced by a mean (+/- SEM) of 82.7 +/- 7.2% (p = 0.012). There was no significant correlation between the protective effect against exercise and that against AMP for individual patients. The percentage change in urinary leukotriene E4 (LTE4) excretion at exercise was + 18.1 +/- 10.9% on placebo and -44.8 +/- 6.2% after ABT-761 (p = 0.017); changes at adenosine were + 38.5 +/- 27.0% on placebo and -36.7 +/- 9.8% after ABT-761 (p = 0.028). On placebo, exercise produced a marked stimulation of the ex vivo LTB4 production, whereas adenosine was associated with only a minor increase; ABT-761 caused a greater than 90% inhibition (p < 0.05 for both challenges). We conclude that ABT-761 is a potent and long-acting 5-LO inhibitor which significantly attenuates exercise- and adenosine-induced bronchoconstriction, indicating that leukotrienes are important mediators in both challenges.

Differential effects of inhaled budesonide and oral prednisolone on serum immunoglobulin G and its subclasses in healthy adult volunteers.

BACKGROUND: Glucocorticosteroid (GCS) treatment lowers serum IgG and IgG subclass (IgG-SC) levels, but the minimal dose and duration of administration at which this occurs is not known. OBJECTIVE: The aim of this study was to define the daily dose of a 2-week course of GCS at which IgG(-SC) suppression occurs. METHODS: The effects of three GCS treatment schemes on serum IgG(-SC) levels in healthy adults were studied in a double-blind, randomized trial. Group 1 (n = 10) was treated with 40 mg oral prednisolone/day, group 2 (n = 10) with 10 mg oral prednisolone/day and group 3 (n = 10) with 3.2 mg inhaled budesonide/day. Blood sampling was performed at baseline and at the end of the 2-week treatment period. RESULTS: In group 1, IgG1, IgG2 and IgG3 levels were significantly decreased after treatment, while in group 2 this was only so for IgG3. In both groups, the decrease of total IgG tended towards or just reached significance. In group 3, no statistically significant changes were observed. CONCLUSION: A course of 40 mg oral prednisolone/day for 2 weeks induces significant suppression of serum IgG-SC levels; lower doses cause more subtle changes, indicating that GCS-induced IgG-SC suppression is a dose-dependent phenomenon. Short courses of very high doses of inhaled budesonide appear to be devoid of this side-effect.

Analysis of paediatric prescribing profiles in two health-funding systems.

OBJECTIVE: To investigate the adequacy of two large South African medical administrative databases in providing prescribing profiles for paediatricians and general practitioners (GPs) respectively. DESIGN: Statistical analysis of data captured during 1994. Data were analysed retrospectively with frequency analysis and non-parametric tests. SETTING: Two industry databases, one covering a prepaid health maintenance organisation (HMO), the other providing a chronic medication programme for medical schemes and their members. MAIN OUTCOME MEASURES: Comparison of prescribing profiles of specialists and GPs. MAIN RESULTS: Data from the HMO revealed that referrals to paediatricians were mainly for gastro-intestinal and respiratory problems. Paediatricians' prescriptions for treatment of gastro-oesophageal reflux and/or abdominal pain represented 15.5% of all items prescribed and accounted for 40.7% of total paediatric medicine costs. GPs used formulary items more frequently, and cost per prescription was two-thirds that of specialists. Data from the chronic medication programme were used to compare treatment of asthma by the two provider groups. There were significant differences in the prescribing profiles of the two groups, with specialists using more in the way of "third-line agents' and newer, expensive products. Significant numbers of prescriptions did not conform to national guidelines for treatment of asthma. CONCLUSIONS: Industry databases provide a viable and valuable source of information; however, some problems were experienced in extracting the required data. Prescribing profiles revealed certain practices that require review, in particular the relatively low use of generic products, the early resorting to drug therapy for gastrooesophageal reflux, and non-conformity with national guidelines for management of childhood asthma.

The effect of inhaled FK224, a tachykinin NK-1 and NK-2 receptor antagonist, on neurokinin A-induced bronchoconstriction in asthmatics.

The tachykinins substance P and neurokinin A (NKA) are present in sensory airway nerves and have been implicated in the pathogenesis of asthma. FK224 is a cyclopeptide tachykinin antagonist previously shown to inhibit both tachykinin NK-1 and NK-2 receptor mediated airway responses in guinea pigs. Inhaled FK224 protected against bradykinin-induced bronchoconstriction and cough in asthmatics. In this study we examined the reproducibility of the NKA challenge and the effect of inhaled FK224 on NKA-induced bronchoconstriction in 10 patients with stable asthma. On Day 1 baseline lung function and PC20 methacholine were determined. On Days 2 and 3 increasing doubling concentrations of NKA (3.3 x 10(-9) to 1.0 x 10(-6) mol/ml) were administered via inhalation, with intervals of 10 min. On both days NKA caused a concentration-dependent decrease in specific airways conductance (sGaw) and FEV1. Mean +/- SEM, log PC35, sGaw NKA (mol/ml) was -6.61 +/- 0.10 on Day 2 and -6.57 +/- 0.14 on Day 3 (not significant [NS]). On Days 4 and 5 FK224 (4 mg) or placebo (P) was administered via metered-dose inhaler 30 min before NKA challenge in a double-blind, crossover manner. The study medication was well tolerated. FK224 had no significant effect on baseline lung function. After P and FK224, NKA caused a comparable concentration-dependent bronchoconstriction. The mean +/- SEM log PC35 sGaw NKA (mol/ml) was -6.04 +/- 0.18 after P and -6.19 +/- 0.23 after FK224 (NS). In conclusion, inhaled FK224 had no effect on baseline lung function and offered no protection against NKA-induced bronchoconstriction in a group of mild asthmatic patients.

Short courses of high-dose inhaled budesonide and serum IgG subclass levels in healthy volunteers.

BACKGROUND: The incidence of systemic side effects of inhaled budesonide increases at doses exceeding 2000 micrograms/day. OBJECTIVE: This study was carried out to investigate whether high-dose inhaled budesonide affects serum IgG subclass concentrations in healthy adult volunteers. METHODS: Two groups of 10 subjects each inhaled 2.4 mg of budesonide per day in a double-blind, crossover study of morning (8:00 AM and noon, group A) and diurnal (8:00 AM and 8:00 PM, group B) dosing schedules for 4 weeks each, separated by a 2-week washout period. The budesonide was inhaled through a pressurized metered-dose inhaler, mounted on a 750 ml Nebuhaler (ASTRA Pharmaceuticals, Lund, Sweden). The IgG subclass levels were determined at baseline and every 2 weeks until the end of the study period (10 weeks). RESULTS: There were no statistically significant changes in the serum IgG subclass concentrations over the 10-week study period in group A, group B, or groups A and B combined. CONCLUSION: Inhalation of budesonide, 2.4 mg/day, through a large-volume spacer for repeated 1-month periods does not influence serum IgG subclass concentrations in healthy adults, suggesting that budesonide does not cause systemic humoral immunosuppression when given at therapeutic doses.

Non-Hodgkin's lymphoma presenting as multiple cavitating pulmonary nodules.

Intrathoracic involvement is common in non-Hodgkin's lymphoma (NHL). We present the case of a young woman with a secondary pulmonary lymphoma (SPL) of the centroblastic subtype, with B-cell characteristics. The chest radiograph at presentation revealed an extremely rare pattern of multiple cavitating pulmonary nodules. The radiographic patterns of intrathoracic NHL are discussed.

Malaria prophylaxis--the South African viewpoint.

A consensus meeting was held under the auspices of the Department of National Health and Population Development in September 1991 in order to establish local, current consensus on malaria prophylaxis for the South African traveller within South Africa and neighbouring African countries. The meeting was attended by malaria experts and others interested in malaria. The consensus reached took into consideration not only the international literature, but also local clinical experience and viewpoints. As a result, it was decided that prevention of mosquito bites is the mainstay of malaria prophylaxis and that chemoprophylaxis should be individualised. Malaria may still be contracted despite good compliance with the recommended prophylactic regimen.

Tracheobronchomegaly--the Mounier-Kuhn syndrome: report of two cases and review of the literature.

Tracheobronchomegaly (TBM) is a rare disorder of uncertain aetiology, characterized by marked dilatation of the trachea and main bronchi, bronchiectasis and recurrent lower respiratory tract infections. Two patients with TBM are presented. In one case, a marked decrease of elastic and smooth muscle tissue was present in the bronchial biopsy specimens, obtained by rigid bronchoscopy. The airways of the second patient were visualized using computed tomography. The dimensions of the airways of our patients are compared with the normal values supplied in the literature.

Adamantinoma of the tibia with pulmonary metastases and hypercalcemia.

Adamantinomas of long bones are rare primary malignant bone tumors. A case of a woman who died of pulmonary metastases of an adamantinoma of the tibia is presented. A unique feature of this case is the association with hypercalcemia. The association of hypercalcemia, hypophosphatemia, decreased parathyroid hormone levels and increased urinary cAMP excretion suggests a humorally mediated hypercalcemia. Histologic and ultrastructural analysis of the pulmonary metastases demonstrated that the tumor was composed of a heterogeneous cell population with mesenchymal and epithelial differentiation.

Neuropsychological deficit and emotional disturbance in head-injured patients.

The relationship between neuropsychological deficit and emotional disturbance was examined in a sample of 124 patients who sustained work-related head injuries. Most injuries met criteria for minor head injury. Since all patients were receiving compensation, the relationship between emotional disturbance and neuro-behavioral deficit does not appear to be related to compensation or litigation factors. There was a positive relationship between degree of neurobehavioral and emotional abnormality. This was not due to the interval between injury and examination, and did not appear to be related to duration of unconsciousness or amnesia, or to the presence of skull fracture or posttraumatic seizures. The findings are discussed in relation to previous research and to their implications regarding posttraumatic emotional adjustment.

Rehabilitation of the injured worker.

The Workers' Compensation Board is mostly involved in secondary and tertiary prevention of work-related accidents and disease. Through its new Medical Rehabilitation Strategy, the board will help to ensure that optimal health care programs are available to injured workers. For workers who are left with restricted function, even after the best possible health care, vocational rehabilitation or tertiary prevention programs are offered. In both phases the primary care physician has a key function and must be familiar with the "state of the art" treatment of so-called minor trauma and activity-related disorders. Physicians also must recognize the importance of providing a reasonable prognosis as early as possible because it will drive the vocational rehabilitation planning process.