Guidelines for nonspecific bronchial provocation tests

This study evaluated the effects of a predialysis patient education programme on functioning and well-being in 28 uraemic patients. The programme consisted of four group sessions with the following themes: renal disease and dietary restriction, active renal replacement therapy, physical exercise, and the impact of chronic renal failure on economy, family and social life. Three to 9 months after having started dialysis the patients were evaluated regarding symptoms, perceived health (Health Index), functional (SIP) and emotional (STAI) status. Twenty-eight patients already on dialysis treatment informed according to conventional routines constituted the comparison group. There were no significant differences between the groups regarding age, sex, educational or social background, duration of kidney disease, choice of dialysis treatment, cause of renal disease and laboratory tests except for s-urea. The patients who participated in the education programme scored significantly better mood, less mobility problems (HI), less functional disabilities (SIP) and lower levels of anxiety (STAI) compared to the comparison group. There were no significant differences between the two groups regarding symptoms and overall health. The differences between the groups prevailed during the first 6 months on dialysis treatment, after which the differences disappeared. In the comparison group age correlated significantly to anxiety and overall SIP, which was not the case in the experimental group. In conclusion, the experimental group that participated in a predialysis patient education programme, showed better functional and emotional well-being than the non-educated comparison group. The positive effects of participating in an education programme prevailed during the first 6 months of dialysis treatment. Moreover, the younger patients seemed especially to benefit from participation in a predialysis patient education programme. It is suggested that patient education should be ongoing for patients with end-stage renal failure initiated during the predialysis stage and continued after maintenance dialysis has been established.     

Bronchodilator response to salbutamol after chronic dosing with salmeterol or placebo

OBJECTIVES: We report the occurrence of cardiac events during long-term follow-up in patients with hypertrophic cardiomyopathy (HCM) after cardioverter-defibrillator implantation. BACKGROUND: The identification of patients at high risk for sudden death and the prevention of recurrence of sudden death in HCM represents a difficult problem. METHODS: We retrospectively analyzed the occurrence of cardiac events during follow-up of 13 patients with HCM who received an implantable cardioverter-defibrillator (ICD) because of aborted sudden death (n = 10) or sustained ventricular tachycardia (n = 3) (group I). Findings were compared with those in 215 patients with an ICD and other structural heart disease or idiopathic ventricular fibrillation (group II). RESULTS: After a mean (+/-SD) follow-up period of 26+/-18 months, 2 of 13 patients in group I received appropriate shocks. The calculated cumulative incidence of shocks was 21% in group I and 66% in group II after 40 months (p < 0.05). We observed a low incidence of recurrence of ventricular tachycardia/fibrillation during follow-up in patients with HCM. No deaths occurred. CONCLUSIONS: Our data suggest that ventricular tachyarrhythmias may not always be the primary mechanism of syncope and sudden death in patients with HCM. The ICD seems to have a less important impact on prognosis in patients with HCM than in patients with other etiologies of aborted sudden death.     

Specific bronchial provocation tests with flour in the diagnosis of occupational bronchial asthma

The gold standard in the diagnosis of occupational asthma is the specific bronchial provocation test (sBPT), but other diagnostic criteria have been proven to have a similar sensitivity, mainly in asthma due to high molecular weight compounds. In order to assess wether some clinical findings can predict the positive response to sBPT, we studied 37 subjects (14 millers and 23 bakers) with suspected occupational asthma who underwent sBPT with wheat flour dust (dust exposure in a small cabin: geometric mean 12.1 mg/m3 for up to 30 min). A positive response to sBPT (FEV1 > 20%) was elicited in 20 subjects (11 early, 4 late, and 5 dual responses). There was no significant difference between subjects with positive or negative sBPT as regards mean age, smoking, length of employment, duration of symptoms, atopy (skin positivity to one or more common allergens) and PD20FEV1 methacholine. The percentage of subjects with work-related symptoms was significantly higher in subjects with positive sBPT with respect to subjects with negative sBPT (81% versus 41.2%, p < 0.01 by chi 2 test); furthermore, FEV1 was significantly lower in subjects with positive sBPT. The percentage of positive skin response to wheat flour extract (mean wheal diameter > or = 3 mm) was mildly but not significantly higher in subjects with positive sBPT (68.4% versus 41.2%). None of the following clinical factors (age < 35 years, asthma symptoms pre-existing occupational exposure, non smokers, atopy and bronchial hyperresponsiveness to methacholine), alone or in combination, were associated with higher prevalence of positive sBPT. We conclude that the response to sBPT in subjects with suspected occupational asthma due to flour dust can not be adequately predicted by other clinical, allergologic and functional data. Therefore, sBPT with flour dust should always be performed in subjects with suspected occupational asthma.     

Bronchodilator response to nebulized salbutamol in elderly patients with stable chronic airflow limitation

The bronchodilator response to 5 mg nebulized salbutamol was studied in 20 elderly patients with stable chronic airflow limitation. Salbutamol produced significantly greater increases in FEV1 and FVC compared with placebo although there was no difference in subjective sensation of breathlessness. Spirometry can be successfully used to assess respiratory function in appropriately selected elderly patients with chronic airflow limitation.     

The specific bronchial provocation test in the diagnosis of occupational asthma

Specific bronchial challenge (SBC) testing is a key technique for diagnosing the origin of occupational asthma (OA). SBC is indicated in specific circumstances, including whenever several agents present in the work environment may be the cause of OA, when new or unusual occupational agents need to be identified, when evidence for legal action is required, or when research is conducted. SBC procedures are not standardized, because of the great diversity of occupational agents and the variety of physical and chemical properties involved. Thus, SBC testing with agents found in fumes, gases or vapors can be administered in special cabins or in closed circuits with continuous monitoring of sub-irritant concentrations. Agents found in dust, most but not all of which have high molecular weights, may be appropriate for routine SBC testing in an allergy laboratory. This paper will treat only these cases. SBC must be formed in specialized centers by experienced personnel, as it is a sophisticated and potentially dangerous technique. We describe a series of 20 patients diagnosed of OA in our unit over the past two years in whom SBC provided an etiologic diagnosis. All were exposed to dust or aerosols at work. The cause was a substance of high molecular weight in 17 cases, and low molecular weight in 3. The procedure used is described and models of bronchial response are discussed.     

The immediate and late allergic response to segmental bronchopulmonary provocation in asthma

The response to antigen is an important factor in the development of airway inflammation. Segmental bronchoprovocation (SBP) with antigen and subsequent bronchoalveolar lavage (BAL) have provided valuable insight into the mechanisms of allergic inflammation. To determine the features of allergic airway response in asthma, 19 subjects with mild asthma underwent antigen SBP in a dose-dependent manner. The amount of antigen used in SBP was 0 (saline), and 1, 5, or 20% of the antigen dose required to drop the FEV1 by 20% (APD20). BAL was done at 5 min and 48 h after SBP. BAL histamine levels increased modestly 5 min after antigen SBP. At 48 h, there was a marked increase in eosinophils and IL-5 concentration even in airway segments where the release of histamine was small. Moreover, eosinophils correlated with IL-5 levels at 48 h (r = 0.63; p < 0.001), but not with BAL histamine concentrations at 5 min. GM-CSF levels did not increase after antigen SBP and did not correlate with eosinophils. These observations indicate that asthmatic subjects can develop a dose-dependent response to antigen SBP that is characterized by a modest increase in histamine immediately after antigen exposure, and marked eosinophilia, which appears proportionately greater than the histamine response and relatively greater than what is seen in allergic nonasthmatic subjects. This feature might be important to the eventual development of airway inflammation in asthma.     

Hypokalaemia following nebulized salbutamol in children with acute attack of bronchial asthma

OBJECTIVE: To determine whether use of nebulized salbutamol therapy for treatment of an acute attack of asthma in children is associated with hypokalaemia and if so what is its frequency, severity and effect on recovery. METHODOLOGY: Forty-six children, aged 10 months to 12 years (mean 7.9 +/- 1.5 years) with acute attack of bronchial asthma, treated initially with three doses of nebulized salbutamol 0.15-0.3 mg/kg, every 30 min participated in the study. Blood for serum potassium was obtained at the beginning and after three doses of nebulized salbutamol therapy, before administering other drugs. RESULTS: The mean +/- SD serum potassium level decreased marginally from 3.9 +/- 0.5 mEq/L to 3.7 +/- 0.5 mEq/L (P < 0.05). A decrease in serum potassium concentration was noted in 26 (56.5%) and hypokalaemia (serum potassium < 3.5 mg/L) in 17 (39%) patients. It was more frequent in patients who had received oral salbutamol for the preceding 7 days. The average time taken for recovery was longer in patients who had hypokalaemia than those who had normal serum potassium concentration (8.6 +/- 2.7 h vs 6.5 +/- 2.7 h; P < 0.005). CONCLUSIONS: Hypokalaemia may occur in about one-third of patients treated with three doses of nebulized salbutamol therapy, especially those on prior oral salbutamol therapy. The monitoring of serum potassium concentration may be warranted in such patients.     

Is it possible to predict the result of the bronchial provocation test in children with asthma?

Bronchial hyperreactivity (BHR) to different allergic and non-allergic stimuli is characteristic feature of asthma. Sometimes however it is not possible to perform bronchial provocation test (BPT) assessing reactivity. It was interesting for us if the result of BPT can be predicted on the base of routine lung tests. The aim of the study is evaluation of the relationship between BPT results and baseline lung function tests assessing small bronchi obstruction in children suffering from asthma. Investigated group comprised 139 children aged 7 to 17 years, with episodic, mild or moderate asthma. During bronchial challenge lung function was assessed on the base of spirography and maximal flows at 50% and 25% of forced vital capacity (MEF50 and MEF25) and other indices as surface under end-half of flow-volume curve and mean flow times T50 and T25. The study results confirmed good correlation between BPT result and baseline lung function. Those children which had worse initial lung tests had more pronounced bronchial hyperreactivity. This relationship was the closest in the group of children with small bronchi obstruction. Analysis of correlation showed highly significant relationship between baseline lung function tests and degree of bronchial reactivity. The highest significance was observed for MEF50 and MEF25. We conclude that small bronchi test disturbances in children with asthma could predict with high probability results of bronchial challenge.     

New approaches to evaluation of nonspecific inhalation provocation (dose-response relationship) in the comparative evaluation of bronchial hyperreactivity within the scope of clinical trials

For the performance of clinical drug trials in the therapy for bronchial hyperresponsiveness, unspecific inhalatory provocation tests are generally employed to judge therapeutic success. In particular, the parameter-specific provocation doses are considered to be the main target values. However, it must be considered that these provocation doses are not equally calculable for every patient in the same way and at any examination time. This leads to the fact that the number of evaluable case studies is often appreciably lower than the number of test participants and that a meaningful therapy group comparison may even not be possible under certain circumstances. An evaluation model is presented here in order to fully exploit the obtained data; in this the percentile changes of the function parameters (estimated by linear regression) at a defined dose of the provocation substance are analyzed. In analogy, a survival time model and, as a supplement, a best case/worst case analysis are performed for further statistical evaluation. With the present procedure, an evaluation with inclusion of all test participants is possible. In contrast to the previously used evaluation procedures, this allows a reliable statistical confirmation of the results of clinical tests in the therapy for bronchial hyperresponsiveness.     

Metered-dose inhaler to deliver methacholine in bronchial provocation testing: a pilot study

BACKGROUND: Nonspecific bronchial provocation tests may be simplified by the use of hand-held devices to deliver methacholine. OBJECTIVE: To study the feasibility of using a metered-dose inhaler (MDI) to administer methacholine in bronchial provocation tests, and the ability of such a device to diagnose bronchial hyperresponsiveness (BHR) accurately. METHODS: In an open randomized crossover pilot study, we compared the provocative dose that induces a 20% fall in FEV1 (PD20 FEV1) obtained with the methacholine MDI with that obtained using a conventional nebulizer in 20 hyperresponsive and 20 nonhyperresponsive subjects. The MDI delivers 400 doses of 100 microg of methacholine, and was used via a spacer. Bronchial hyperresponsiveness (BHR) was defined as a PD20 FEV1 <2,000 microg with the conventional test using the nebulizer. The tests were performed in each subject in a randomized order, 1 to 7 days apart. RESULTS: Of the subjects who had a nebulizer PD20 FEV1 <2,000 microg, all but one had an MDI PD20 FEV1 <800 microg. When 800 microg was taken as the threshold for the diagnosis of BHR with the MDI test, the accuracy of this test to diagnose BHR was 97.5%, and the two tests were highly concordant for the diagnosis of BHR (Pearson chi2, 36.19; p<0.0001). CONCLUSION: A hand-held device may be suitable for delivery of methacholine during bronchial provocation tests, if these results are confirmed in large samples.     

Increase in non-specific bronchial hyperresponsiveness without specific response to isocyanate in isocyanate-induced asthma: a pilot study

Increased non-specific bronchial hyperresponsiveness (BHR) has been reported after positive reaction to isocyanates in patients with isocyanate-sensitive asthma. The increased responsiveness may, however, also precede the asthma attack. We therefore compared non-specific BHR to a cholinergic agent before and after exposure to toluene-diisocyanate (TDI) that induced no asthma symptoms in 11 workers with isocyanate-related asthma. Patients were exposed for 3 consecutive days to progressively increasing doses of TDI (5, 10, and 20 ppb min-1 for 20 min) in an exposure chamber with continuous TDI monitoring. No immediate nor late asthmatic bronchial reaction was observed in any patient after any dose of TDI during or after challenge. A significant increase in non-specific BHR was noted 24 h after the last dose of TDI challenge, however. This increase was at least one doubling dose for seven of 11 patients. In conclusion, our study shows that, in patients with isocyanate-induced asthma, exposure to TDI induces a slight but significant increase in non-specific BHR in the absence of any immediate or late bronchial response to isocyanate. This result, which requires further confirmation, may justify a proposal to measure non-specific BHR, even after a negative specific inhalation test to TDI, as an additional diagnostic element for TDI-induced occupational asthma, to help lower the percentage of the undetected occupational asthma cases.     

The effect of nedocromil sodium on the clinical course, ventilatory parameters and nonspecific bronchial hyperreactivity in patients with nonatopic bronchial asthma treated with beclomethasone dipropionate

The efficacy of nedocromil sodium (NED) (8mg twice daily) in controlling the clinical symptoms of asthma (score symptoms), the pulmonary parameters (FEV1, FVC) and bronchial hyperreactivity to histamine was assessed. The study was performed in double-blind, cross-over and placebo-controlled way in 16 patients suffering from nonatopic, stable, moderate asthma treated with beclomethasone dipropionate (from 400 micrograms to 800 micrograms). NED and placebo were administered in a randomized way with 8-week wash-out period. Bronchial reactivity to histamine, was measured as the amount of histamine causing a 20% fall in FEV1 (PC20H in mg/ml). Treatment with NED did not change asthma symptom scores, FVC and FEV1. Decreased usage of beta 2-agonist was observed. NED did not influence bronchial hyperreactivity to histamine (xg PC20H was respectively 0.09 and 0.11 mg/ml after placebo and 0.06 and 0.08 after NED). The authors conclude that studies with NED in nonatopic asthmatics should be continued, but the dosage of the drug ought to be bigger and the time of treatment ought to be longer.     

Analysis of T-cell activation after bronchial allergen challenge in patients with atopic asthma

BACKGROUND: T helper cells are a heterogeneous group of cells that have phenotypic and functional differences. Activated T helper cells have been found in peripheral blood after allergen challenge of subjects with atopic asthma, but the phenotypes of specific T helper subpopulation involved remains to be identified. OBJECTIVE: To characterize the T cell activation markers that may be regulated by allergens, we analyzed peripheral blood lymphocytes obtained before and after allergen challenge from subjects with atopic asthma. METHODS: We analyzed the distribution of the cell surface activation markers, interleukin 2 receptor (IL-2R) and major histocompatibility complex class II antigens (MHC II) among T helper subpopulations classified as naive (CD45RA) or memory (CD45RO) phenotypes. Nine adult subjects with atopic asthma underwent bronchoprovacative allergen inhalation and isocapnic cold air hyperventilation (ISH) challenge followed by serial spirometry. Peripheral blood mononuclear cells (PBMC) were isolated at baseline and 2 and 24 hours after challenge. Four-color flow cytometry was used to analyze the expression and distribution in vivo of IL-2R and MHC II activation markers on naive and memory T cell subsets after challenge. RESULTS: At 2 and 24 hours after allergen challenge, there was a significant increase in the CD45RO+IL-2R+ T helper cells compared with baseline (mean +/- SE, baseline, 12.5% +/- 1% versus 2 hours, 18.1% +/- 1% and 24 hours, 17.8% +/- 2%, p < 0.025). MHC II expression was not significantly increased after challenge on naive and memory T helper cells and coexpression of IL-2R and MHC II was only found in a small proportion of CD45RO+ T helper cells (2.7% +/- 1%). No changes of IL-2R or MHC II expression on T helper subsets were observed after ISH challenge in the same patients. We also found that 31% to 46% of T helper cells coexpress CD45RA and CD45RO simultaneously, and upregulation of IL-2-R and MHC II expression occurs only on those T helper cells that express CD45RO. CONCLUSIONS: We have found that T helper cells express both CD45RA and CD45RO isoforms, which suggests the existence of a transitional phenotype among naive and memory T helper cells in peripheral blood. In subjects with atopic asthma, our in vivo analysis characterizes two populations of activated memory T helper cells based on the expression of IL-2R or MHC II surface molecules after allergen challenge.     

The effects of prednisolone on the cutaneous tuberculin response in patients with corticosteroid-resistant bronchial asthma

We have used the classical tuberculin cutaneous delayed hypersensitivity immune response to investigate the effects of corticosteroids on mononuclear cell function in nine subjects with corticosteroid-resistant asthma (CRA) and six subjects with corticosteroid-sensitive asthma (CSA), who demonstrated sensitivity to intradermal purified protein derivative (PPD) of Mycobacterium tuberculosis. In a double-blind, crossover, placebo-controlled study, patients were given oral prednisolone or placebo, starting on day 0, and a predetermined intradermal dose of PPD on day 7. On day 9 the site of the induration was measured and biopsied for immunohistochemical analysis. There was no difference in skin induration between the CSA and CRA groups during the placebo arm of the study (p = 0.38). Prednisolone significantly suppressed the cutaneous induration (p, 0.003) in the CSA group but not in the CRA group. As compared with placebo, the number of macrophages (p = 0.018), eosinophils (p = 0.009), and T memory cells (p = 0.009) was suppressed by prednisolone in the CSA group but not in the CRA group. No significant suppression of the number of neutrophils or monocytes/immature macrophages was induced by prednisolone in either group. There was no difference in intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1 expression in blood vessels or epidermis between the CSA and CRA groups, with no suppression by prednisolone in either group. These findings suggest a defect in the responsiveness of cellular immune mechanisms to the suppressive effects of corticosteroids in steroid-resistant asthma. The differential suppressive effects of corticosteroids on cellular recruitment in the PPD response between the individuals with CSA and those with CRA are not due to modulation of expression of endothelial adhesion molecules.     

Disinhibition and spontaneous recovery of response decrements produced by free reinforcement in rats.

Conducted 3 experiments with a total of 16 Holtzman albino and 48 hooded male rats. After the Ss had been trained to barpress on a variable interval schedule of reinforcement, response rates were reduced by the introduction either of extinction or of a response-independent (free) reinforcement schedule. Spontaneous recovery was consistently obtained in extinction, especially when session durations were long. Under free reinforcement conditions there was little sign of spontaneous recovery, even when with high reinforcement rates response reduction was almost as rapid as in extinction. In disinhibition tests the introduction of noise produced increased responding under free reinforcement conditions but not in extinction. Results are interpreted as demonstrating a dissociation between spontaneous recovery and disinhibition. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differences in response of patient's blood cells with bronchial asthma to diverse house dust mite allergens by histamine release assay

A HPLC method was developed for the determination of histamine released from washed blood cells of allergic patients after exposure to allergens in the presence or absence of plasma. The blood cells used were preserved in a vital state at 4 degrees C during at least 6 hours after blood-collecting. The responses of blood cells to an appropriately diluted series of a mite feces extract (Dff) solution were evaluated in three patient's groups (68 cases of hyposensitized, 59 cases of newly visited and 44 cases of the others) with bronchial asthma. Washed blood cells from the hyposensitized groups had a tendency to release histamine easily even with lower concentration of the Dff solution. Both the sensitivities of washed blood cells to Dff or mite body extract (Dfb) and the responses of the cells to diverse antigens in neither extract differed largely in individual cases. The titer of blocking antibody could be expressed as the amount proportional to the concentration of Dff or Dfb.     

Allergic bronchopulmonary aspergillosis in a patient with no symptoms of asthma until after bronchial lavage

An asymptomatic 56-year-old man was admitted to our hospital because of an abnormal shadow on a chest X-ray film. Allergic bronchopulmonary aspergillosis was diagnosed on the basis of five findings: eosinophilia, immediate skin reactivity to Aspergillus antigen, the presence of precipitating antibodies against Aspergillus antigen, a high concentration of IgE in serum, and central bronchiectasis. He had no symptoms of asthma at the time of diagnosis, but did a few days after he underwent bronchial lavage. We speculate that the asthma attack was related to the bronchial Lavage as follows: First, drainage of mucus plugs by bronchial lavage may have exposed the bronchial epithelium, which had already been sensitized, to aspergillus antigens. Second, the scattered antigen may have dose-dependently stimulated the bronchi. Third, the infection may have increased bronchial responsiveness to the antigen. Symptoms of bronchial asthma are not necessary for the diagnosis of allergic bronchopulmonary aspergillosis.     

Interhemispheric transfer after spontaneous recovery in 43 cases of severe closed head injury.

Examined the possibility of frequent callosal disconnection following closed head injury. Interhemispheric transfer was evaluated in 43 severe closed-head-injured patients (aged 18–51 yrs) using a wide-ranging battery of untimed behavioral tasks, after the period of spontaneous recovery. Only 1 S showed signs of callosal disconnection. Much effective interhemispheric transfer occurred in closed-head-injured Ss after the period of spontaneous recovery. More frequent occurrence of the disconnection syndrome in its acute phase is a possibility that cannot be excluded. (PsycINFO Database Record (c) 2010 APA, all rights reserved)