Bronchial reactivity in hyperresponsive patients and healthy individuals: demonstration with high resolution computed tomography.

OBJECTIVE: High resolution computed tomography (HRCT) was used to assess the extent of bronchial reactivity after inhalative bronchoprovocation and dilation in hyperresponsive patients and healthy subjects. PATIENTS AND METHODS: Patients with mild intermittent asthma, 15 with a >20% decrease in FEV1 and a >10 mmHg (PC20+) in PaO2, 12 with a <20% decrease in FEV1 and a >10 mmHg (PC20-) in PaO2 after provocation, and eight healthy humans were included in the study. Changes in cross-sectional area in a total of 1256 bronchi and in bronchial wall area (792 bronchi) were evaluated after histamine-triggered bronchoprovocation and salbutamol-induced bronchodilation at high lung volumes (FVC 80%). Data were compared with the results of pulmonary function tests (FEV1, PaO2, PaCO2). RESULTS: In all groups, a significant decrease in bronchial cross-sectional area (P<0.001) and a significant increase in bronchial wall area (P<0.001) were observed subsequent to bronchoprovocation. After bronchodilation, the increase in cross-sectional area (P<0.001) and the further increase in airway wall area (P<0.01) were significant in all groups. In PC20+ and PC20- asthmatics, significant differences (P<0.05) in PaO2, >10 mmHg between baseline and provocation were observed. In healthy persons, the PaO2 decrease was <10 mmHg (P>0.05). After histamine provocation, the decrease in FEV1 was measured in the PC20+ group, whereas a <20% FEV1 decrease was found in the PC20- and the control groups, respectively. No significant correlations were observed between radiological data and the results of pulmonary function tests. CONCLUSIONS: HRCT demonstrated bronchial reactivity in hyperresponsive patients and, unexpectedly, in healthy subjects. The applied pulmonary function tests failed to characterize bronchial reactions in the healthy subjects. Based on these results, HRCT is a useful tool by which to achieve a comprehensive understanding of the pathophysiological processes in asthmatic patients.

[HRCT and bronchial asthma: visualization of the pathophysiologic changes of the pulmonary parenchyma after inhalation provocation]. / HRCT und Asthma bronchiale: Visualisierung pathophysiologischer Veränderungen des Lungenparenchyms nach inhalativer Provokation.

PURPOSE: To characterize parenchymal lung affections morphologically in patients with asthma and healthy subjects by high -resolution computed tomography (HRCT) subsequent to histamine-triggered inhalation bronchoprovocation and salbutamol-induced broncholysis, and to compare the results with pulmonary function tests. MATERIALS AND METHODS: Fifteen asthmatics with bronchial hyperreactivity, with a > 20% decrease in FEV1 and a > 10 mmHg decrease in PaO(2) after bronchoprovocation (PC20%+), twelve asthmatics with a < 20% decrease in FEV1 and a > 10 mmHg decrease in PaO(2) after bronchoprovocation (PC20%-), and eight healthy persons without bronchial hyperreactivity underwent inhalation bronchoprovocation and broncholysis. Spirometer-triggered HRCT at high lung volumes was performed, and total and peripheral lung densities and the amount of solid lung structures, representing predominantly vessels, were measured. RESULTS: After bronchoprovocation, we observed significant decreases in total and peripheral lung densities in all groups (p < 0.0005), and a significant increase in lung densities subsequent to bronchodilation (p < 0.0002). The morphological alterations in solid lung structure were not significantly different after bronchoprovocation or broncholysis (p > 0.05), as compared to the baseline measurements. In hyperreactive patients, PaO(2) significantly decreased after provocation and significantly increased after lysis (p < 0.05). In PC20%+ asthmatics, a mean reduction of 27.8% in FEV1 was observed, which was < 20% in the other groups. No significant correlations were observed between radiological data and the results of pulmonary function tests. In healthy persons, we demonstrated highly significant parenchymal response to bronchoprovocation and broncholysis, which was not otherwise documented by pulmonary function tests. CONCLUSION: In both PC20%+ and PC20%- patients as well as in healthy individuals, HRCT was efficient in the evaluation of pathoanatomical alterations of the lung parenchyma subsequent to inhalation provocation. In healthy individuals, these parenchymal alterations were not documented by pulmonary function tests.

Bronchial asthma causing symptoms suggestive of angina pectoris.

Many patients undergoing pharmacological stress echocardiography for assessing symptoms suggestive of coronary artery disease are found to have a normal test. This study was performed to evaluate whether asthma symptoms simulate angina pectoris. A total 41 consecutive patients who had a negative pharmacological stress echocardiography and had been evaluated for angina pectoris were studied. Patients with previously known coronary artery disease or obstructive lung disease were excluded. Lung function testing was performed and the authors proceeded either with the administration of a bronchodilator or with methacholine challenge testing. A questionnaire was applied to assess the symptoms dyspnoea, chest tightness and substernal burning at the end of the challenge test. In addition, patients were asked if they were experiencing those symptoms that made them seek medical attention. From the 41 patients tested, 26 patients showed a significant bronchial hyperreactivity (mean +/- SD provocative concentration causing a 20% fall in the forced expiratory volume in one second 5.93 +/- 4.50 mg x mL(-1)). A total of 20 patients confirmed having those symptoms that led to cardiac evaluation. It was concluded that symptoms suggestive of angina pectoris might represent bronchial asthma. This should be considered in the differential diagnosis of angina pectoris.

Efficiency of continuous positive airway pressure versus theophylline therapy in sleep apnea: comparative sleep laboratory studies on objective and subjective sleep and awakening quality.

Sleep apnea is the most common sleep-related breathing disorder characterized by repetitive episodes of hypoxemia. Therapies include behavioral, surgical, orthodontic, pneumological, and pharmacological interventions. The aim of the present study was to compare the efficiency of pneumological therapy by nasal continuous positive airway pressure (CPAP) versus a pharmacological approach with theophylline (Respicur retard(R) 400 mg) on respiratory variables as well as objective and subjective sleep and awakening quality in patients with moderate sleep apnea measured by polysomnography and psychometry. Under CPAP therapy all respiratory variables improved and normalized, while under theophylline only the apnea-hypopnea index and the desaturation index improved but still did not return to normal values. Regarding sleep initiation and maintenance, CPAP therapy prolonged sleep latency and reduced movement time, while patients treated with theophylline showed reduced total sleep period, total sleep time and sleep efficiency. Sleep architecture demonstrated an increase in deep sleep and REM stages under CPAP therapy, and remained unchanged under theophylline. Concerning subjective sleep and awakening quality, both treatments improved well-being in the morning. Regarding objective awakening quality, reaction time performance was improved in both groups. In conclusion, CPAP treatment is more effective than theophylline regarding respiratory variables as well as the normalization of sleep maintenance and sleep architecture in sleep apnea patients.

Severe pulmonary hypertension reversed by antibiotics in a patient with Whipple's disease.

The case is described of a 58 year old man with systemic Whipple's disease with pericardial and pleural effusions and severe pulmonary hypertension. After three months of antibiotic treatment there was a complete resolution, not only of the symptoms known to be associated with Whipple's disease (diarrhoea, arthralgia, pericardial and pleural effusions), but also of pulmonary hypertension.

Effect of solution and suspension type aerosol of formoterol on tremor response and airways in patients with asthma.

BACKGROUND: Aerosol delivery and deposition to the oropharynx and the lungs have been found to be different for solution-type and suspension-type metered-dose aerosols used for treatment of asthma. We investigated possible differences in clinical effects between solution and suspension metered-dose formoterol aerosols. METHODS: A total of 24 patients with asthma (forced expiratory volume in 1 second, < or = 70% predicted) inhaled single doses (12 micrograms or 24 micrograms) of formoterol solution and suspension so that we could investigate the immediate tremor, airway, and cardiovascular responses in a randomized, double-blind, crossover trial. Fenoterol suspension aerosol (400 micrograms) was used for comparison (single-blind, poststudy, nonrandomized administration). Fenoterol (400 micrograms) as a rescue medication was inhaled after 120 minutes on each of the 5 study days. RESULTS: The order of mean (+/- SEM) maximum tremor acceleration was as follows: 12 micrograms formoterol solution (67.92 +/- 4.54 cm x sec-2) < 24 micrograms solution (73.46 +/- 4.51 cm x sec-2) < 12 micrograms suspension (80.87 +/- 5.08 cm x sec-2) < fenoterol (84.13 +/- 4.21 cm x sec-2) < 24 micrograms formoterol suspension 88.54 +/- 6.26 cm x sec-2). Maximum increase in specific airway conductance ranged from 0.48 +/ 0.03 to 0.55 +/- 0.04 sec-1 x kPa-1 for all drugs (p > 0.05). No change in cardiovascular parameters occurred (p > 0.05). CONCLUSION: No difference in the bronchial response to either formulation of formoterol was found. Tremor response to suspension aerosol (24 micrograms > 12 micrograms) was higher than that to solution aerosol (24 micrograms > 12 micrograms), indicating possible differences in systemic absorption because of a different deposition pattern. Rescue medication demonstrated systemic effects on tremor that were additive to those of formoterol.

Comparison of the single breath with the intrabreath method for the measurement of the carbon monoxide transfer factor in subjects with and without airways obstruction.

BACKGROUND: Measurement of the carbon monoxide transfer factor (TLCO) has traditionally been performed using the single breath method but recently the intrabreath method has been developed. The aim of this study was to compare the two methods in the clinical evaluation of patients with obstructive and non-obstructive pulmonary disorders. METHODS: Measurements of TLCO with the intrabreath method were carried out on a study sample composed of 50 patients with non-obstructive disorders and 50 with airways obstruction (FEV1/FVC < 70%) either before or after a single breath measurement of the TLCO had been performed. The method involves the continuous analysis of a single slow expirate using a computerised rapid multigas infrared analyser. TLCO, alveolar volume (VA), TLCO/VA, and inspired vital capacity (IVC) values were obtained for both groups by both methods. RESULTS: When measured with the intrabreath method the group with airways obstruction showed lower TLCO and TLCO/VA values than the non-obstructive group. VA was higher in both patient groups when measured with the intrabreath technique. The same test also showed higher TLCO values with the intrabreath method in the group with non-obstructive disorders and lower TLCO/VA values with the intrabreath method in those with airways obstruction. The corresponding parameters obtained by the two methods correlated closely, with no correlation between the magnitude of the differences with the magnitude of the readings. An index of gas mixing indicated a better distribution of the inspired air for the intrabreath method than for the single breath method. The VA values obtained with the intrabreath method showed a closer agreement to the actual total lung capacities measured by body plethysmography. CONCLUSION: The intrabreath method of determining TLCO is comparable to the traditional single breath method. Measurement of alveolar volume by the intrabreath method approximates more closely to total lung capacity, even in subjects with airways obstruction.

Effects of neuropeptide Y and vasoactive intestinal peptide on human venous smooth muscle in vivo.

The direct and noradrenaline-modulating effects of neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) on venous smooth muscle were studied in healthy volunteers employing the dorsal hand vein compliance technique. Local infusions of NPY had no measurable effect on venous tone, but coinfusion of a constant high dose of NPY (242 pmol/min) with noradrenaline caused a 2.9-fold increase in the mean ED50 for noradrenaline. The dilating effect of VIP on preconstricted hand veins was weak, maximal venodilation could not be achieved, because systemic side effects occurred at submaximally venodilating doses. Coinfusion of noradrenaline with a weakly venodilating, constant dose of VIP (93.2 pmol/min) caused a 0.5-fold decrease in the sensitivity for noradrenaline. Although functional interactions between NPY or VIP and noradrenaline could be demonstrated, the dosages of the peptides required were high. Thus our results indicate that neither NPY nor VIP exert a major direct or noradrenaline-modulating effect on human veins.

Prediction of sensitization to flour allergens.

The purpose of the present study was to investigate the factors that may contribute to the sensitization to flour in baker's apprentices, and to predict this type of sensitization with a stepwise logistic regression model. Of the total of 258 baker's apprentices, 54 (20.9%) exhibited specific IgE development against flour allergens (wheat, rye, and/or barley). Allergologic variables, such as the total IgE level and IgE specific to grass pollen, tree pollen, weed pollen, molds, and animal dander, were found to correlate strongly with the sensitization to flour. However, the correlation between the presence of other manifest allergies and the sensitization to flour was weak. The presence of shadowing of the paranasal sinuses on the radiograph (mucosal thickening, opacity, air/fluid levels, and/or polypous shadowing) correlated with flour sensitization as well as with the leukocyte and lymphocyte counts in peripheral blood. Of the lung function data, only total lung capacity (in percentage of the predicted values) weakly correlated with the sensitization to flour. We were able to predict flour sensitization with a sensitivity of 63%, a specificity of 90%, and an efficiency of 84% by using the parameters that allow for the presence or absence of IgE specific to grass pollen and tree pollen, the presence or absence of radiographic shadowing, and total lung capacity in percentage of the predicted values.

Factors contributing to the occurrence and predictability of bronchial hyperresponsiveness to methacholine in children.

Using a stepwise logistic regression analysis, we investigated clinical data, allergologic findings, spirometric data, and the cellular and humoral immune system in order to gain new insights into the role these parameters play in bronchial hyperresponsiveness to methacholine in children and to create a model for the prediction thereof. Bronchial hyperresponsiveness, which was found in 124 of 462 children (26.8%), was observed to have been influenced by an increased level of eosinophils, the positivity of the skin prick test for any of the allergens tested, a decreased baseline forced expiratory volume in 1 second (FEV1) (percent predicted), a decreased maximum expiratory flow at 50% expiration as a percent of forced vital capacity, and a decreased level of kappa-chain-assembled immunoglobulins. Logit analysis disclosed that the influence of all other parameters on the occurrence of bronchial hyperresponsiveness was of no further statistical significance. The degree of bronchial hyperresponsiveness (provocative dose causing a 20% fall in FEV1) showed a statistically significant correlation with the eosinophil count (Spearman's r = -0.198) and FEV1 (percent predicted) (Spearman's r= 0.203). Our findings suggest that allergic sensitization and eosinophilic reaction in children are major factors in contributing to the occurrence of bronchial hyperresponsiveness to methacholine.

Effects of the sauna on diffusing capacity, pulmonary function and cardiac output in healthy subjects.

The present study examined possible short-term effects of the heat stress during sauna bathing on gas exchange, especially in correlation with changes in cardiac output. The results obtained are as follows: (1) The heat stress of sauna bathing caused a slight but not significant increase in diffusion capacity (p = 0.239) and no change in other pulmonary function parameters. (2) Cardiac output and cardiac index increased slightly but not significantly (p = 0.2455 and p = 0.2719). We conclude that heat stress in sauna neither influences gas exchange nor does it cause a significant increase in cardiac output.

Studies on the bronchodilator, tremorogenic, cardiovascular and hypokalaemic effects of fenoterol dry powder in asthma.

1. The airway and tremor response and cardiovascular and hypokalaemic effects of single and cumulative doses of fenoterol given by dry powder capsules (DPC) and by metered dose inhaler (MDI) were studied in asthmatics in two randomized, crossover trials. 2. Single doses of fenoterol DPC and MDI (0.2 mg, 0.4 mg), investigated in 24 subjects, produced similar, dose-dependent increases in FEV1. Fenoterol DPC caused less tremor response and less hypokalaemic effects than fenoterol MDI. 3. Cumulative doses of fenoterol DPC and MDI (0.2, 0.6, 1.4, 3.0, 6.2 mg), investigated in 12 subjects, produced a comparable bronchodilatation (mean maximum increase in FEV1 was 0.53 +/- 0.06/0.52 +/- 0.081 for DPC/MDI) and a similar, dose-dependent rise in heart rate (35 +/- 3.81/41 +/- 2.25 beats min(-1)). The rise in tremor and the fall in plasma potassium were smaller after DPC than after MDI. The mean maximum changes were 51.58 +/- 6.41/95.83 +/- 6.75 cm s(-2) for tremor and -0.68 +/- 0.09/-0.96 +/- 0.10 mmol l(-1) for potassium. 4. Our findings may result from a difference in the pharmacokinetics of the dry powder and the aerosol formulation, particularly differences in distribution and absorption. 5. In conclusion, fenoterol DPC used in low therapeutic doses (0.2,0.4 mg), is preferable to the MDI. Fenoterol DPC used as rescue medication in high cumulative doses, do not suggest a greater safety margin than the MDI and the same restrictions should be considered for the fenoterol dry powder formulation as suggested for the MDI.

Pharmacodynamic effects of inhaled dry powder formulations of fenoterol and colforsin in asthma.

The airway and tremor response and cardiovascular and hypokalemic effects of single doses of inhalative fenoterol dry powder capsules (0.4 mg) were compared with the fenoterol metered dose inhaler (0.4 mg) and colforsin (forskolin) dry powder capsules (10.0 mg), a direct activator of the adenylate cyclase system, in 16 patients with asthma. Subjects (FEV1 < or = 60% predicted) were investigated in a randomized, double-masked, placebo-controlled, four-period, crossover trial for a 120 minute period. All active drugs caused a significant increase in specific airway conductance (p < 0.05); the order of potency (mean +/- SEM maximum increase from baseline) was fenoterol metered dose inhaler (0.51 +/- 0.06 sec-1 x kPa-1), fenoterol dry powder capsules (0.49 +/- 0.07), and colforsin dry powder capsules (0.30 +/- 0.03). A marked increase in finger tremor amplitude resulted after fenoterol metered dose inhaler only (62.93% +/- 10.21%; p < 0.05) in contrast to fenoterol dry powder capsules (15.84% +/- 4.35%; p < 0.05) and colforsin dry powder capsules (12.87% +/- 10.44%; p > 0.05). A decrease in plasma potassium was found after fenoterol (metered dose inhaler > dry powder capsules; p < 0.05). In conclusion, fenoterol dry powder capsules caused less tremor response and hypokalemic effects than the metered dose inhaler, although the bronchodilator capacity was similar. Colforsin dry powder capsules resulted in a measurable bronchodilatation in patients with asthma.

Allergenic structures in cockroach hypersensitivity.

The tissues from which cockroach allergens were derived were identified by use of serum IgE of five patients with allergic rhinitis and bronchial asthma as a result of hypersensitivity to German cockroach. RAST and skin test results demonstrated four of five patients to be positive to cockroach only, and one patient was tested positive to house dust mite as well. Allergen-specific IgE binding to German cockroach was investigated by cryostat sections by means of immunofluorescent test. In all patients with cockroach hypersensitivity, we found IgE bound to the gastrointestinal epithelium and contents of the intestinal tract. In four cases, IgE was also bound to the Malpighian vessels (equivalent in function to kidneys). In three cases, IgE was also bound to the ovarian cells. All cases revealed cytoplasmic staining.

Increased plasma histamine levels in uraemic pruritus.

1. We determined plasma levels of histamine in uraemic patients and examined their correlation with the presence of pruritus. 2. In 27 patients with chronic renal failure, plasma histamine levels were analysed by radioimmunoassay and were compared with those of 40 healthy adult subjects. The control population showed plasma histamine concentrations of 185 +/- 33 pg/ml, which were significantly lower than those of the patients with renal insufficiency. The highest levels (552 +/- 116 pg of histamine/ml) were found in 16 patients with chronic renal failure (mean serum creatinine 5.1 +/- 1.0 mg/dl) and severe itching. 3. Twelve patients with pronounced pruritus who were on maintenance haemodialysis (serum creatinine 9.2 +/- 1.2 mg/dl) had a mean plasma histamine concentration of 515 +/- 81 pg/ml. Fifteen patients on regular haemodialysis (serum creatinine 9.0 +/- 1.5 mg/dl) and who experienced itching had plasma histamine levels (322 +/- 40 pg/ml) which were significantly lower (P less than 0.01) than those of the patients with pruritus but which were elevated compared with those of the control population (P less than 0.01). 4. No correlation could be found between increased plasma histamine levels and the type of dialysis membrane used or the method of sterilization of the membrane. 5. Haemodialysis alone did not reduce plasma histamine concentrations, although high concentrations could be detected in the ultrafiltrate. In six patients a rapid decrease in plasma histamine concentration from 565 +/- 134 pg/ml to within the normal range could be detected after 60 min of combined haemodialysis and haemoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)