[Recommendations for asthma therapy in children and adults].
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Adolescent↗
Biomedical subjects
H Magnussen
Publications and source records attributed to H Magnussen.
Citric acid-induced cough thresholds in normal subjects, patients with bronchial asthma, and smokers.
Several challenge procedures have been developed to characterize the cough reflex in patients with airway diseases. This study was performed to compare the interindividual range of cough sensitivity in asthmatic and normal subjects as well as smokers using an identical method. Sixteen normal subjects, 20 patients with mild bronchial asthma, 6 patients with moderate to severe bronchial asthma, 9 current smokers, and 7 occasional smokers were included. In all subjects, methacholine challenges and standardized citric acid challenges were performed. Sensitivity of the cough reflex was expressed as cough threshold, i.e., as concentration at which coughing occurred. Reproducibility was assessed in 23 subjects. Within a concentration range of 0.625-320.0 mg/ml, inhaled citric acid caused cough in all subjects. Geometric mean (range) cough threshold was 13 (2.5-160) in normal subjects, 14 (5-40) in patients with mild, and 32 (20-40) mg/ml in patients with moderate to severe asthma, 40 (20-80) in current smokers, and 119 (80-160) in occasional smokers. Cough thresholds were reproducible within one doubling concentration. In normal subjects and patients with mild bronchial asthma, thresholds were not significantly different from each other but lower than those of the other groups (p<0.05 each). Cough thresholds in smokers and patients with moderate to severe asthma did also not differ significantly and were lower than in occasional smokers (p<0.05). There was no significant correlation between cough threshold, baseline FEV subset1 , and methacholine responsiveness. Our data indicate that (1) subjects with mild asthma showed on average similar cough thresholds as normal subjects, (2) there was a large variation in cough thresholds within groups, (3) the reproducibility of cough thresholds was within one doubling concentration, (4) cough thresholds did not correlate with methacholine responsiveness or baseline airway tone. In view of the prevalence of cough as a symptom of bronchial asthma, it appears that the determination of citric acid-induced cough thresholds does not yield additional diagnostic information in these subjects.
Administration, Inhalation↗
Effect of a nasal challenge with endotoxin-containing swine confinement dust on nasal nitric oxide production.
Inhalation of swine confinement dust containing endotoxin causes an inflammatory response in the nose as reflected by an influx of neutrophils 3 hrs after exposure (Am J Respir Crit Care Med 149: A401(1994)). As there is evidence that nitric oxide (NO) in exhaled air indicates cellular activation, we studied whether endotoxin causes an increase in nasal NO production in human subjects. Seven healthy subjects underwent a nasal challenge in which 50 mg swine confinement dust was given into each nostril (endotoxin concentration, 23.6 microg . g-1). Exhaled NO was measured before and during 3 hrs after the challenge and was compared to control values measured over the same period of time. Endotoxin produced a slight but statistically significant (p = 0.017) increase in nasal NO concentrations, mean (+/-SEM) values over 3 hrs being 367.5 +/- 7.5 ppb after endotoxin and 342.1 +/- 7.2 ppb under control conditions. The difference was most pronounced during the first hour after the challenge. We conclude that nasal administration of endotoxin causes a short-term increase in NO production which must precede cell influx or upregulation of transcription.
Adult↗
[Problems in adjustment to negative pressure ventilation].
We tried to establish a nasal intermittent positive pressure ventilation for a 54-year old patient with post-polio kyphoscoliosis. Due to intractable rhinitis the patient stopped the treatment. A negative pressure ventilation via a cuirass exhibited an inverse ventilation: during the inspiratory cycle of the ventilator the diaphragm was elevated and the patient was forced to exhale, afterwards he needs to inhale by himself. The ventilatory support is now done via a combined nasal-mouth mask and intermittent positive pressure ventilation.
Combined Modality Therapy↗
[Prospective study of the quality of life in intermittent self-ventilation].
PATIENTS AND METHOD: We assessed quality of life for 17 patients (age 14 to 74 years) before and during intermittent (nightly) nasal home mechanical ventilation with a standardized questionnaire (SF 36, Medical Outcomes Trust, Boston, USA). Underlying diseases were amyotrophic lateral sclerosis, bronchiectasis, kyphoscoliosis, pulmonary emphysema, muscular dystrophy and sequelae of tuberculosis. Blood gas and lung function data were collected during every examination. RESULTS: We observed statistically significant increases for items of general health, mental health, vitality and capillary oxygen partial pressure. CONCLUSION: The SF 36 allows to assess quality of life for patients under intermittent mechanical ventilation at home.
Adolescent↗
Effect of 3 hours' passive smoke exposure in the evening on airway tone and responsiveness until next morning.
To study the effect of environmental tobacco smoke (ETS) exposure in the evening on nocturnal changes in airway tone and responsiveness, 17 subjects with mild asthma (mean +/- SD age, 26 +/- 5 years, FEV1% pred., 89 +/- 14%) were exposed to either ambient air (sham) or ETS (20 ppm CO) for 3 h (7:00 to 10:00 p.m.). Seven subjects had a history of ETS-induced respiratory symptoms. Spirometry was performed 2 h before exposure (5:00 p.m.), every 30 min during exposure, and at 11:00 p.m., 3:00 a.m., and 7:00 a.m. The provocative concentrations of methacholine necessary to decrease FEV1 by 20%, PC20FEV1, were assessed at 5:00 p.m., 11:00 p.m., 3:00 a.m., and 7:00 a.m. Compared with pre-exposure measurements, mean FEV1 values during and after ETS exposure were significantly lower than with sham exposure = 0.013 and 0.026). This effect, however, was due to a significant response in single individuals. The higher bronchial responsiveness after ETS than after sham exceeded one doubling concentration in 4, 5, and 4 patients at 11:00 p.m., 3:00 a.m., and 7:00 a.m., respectively. The opposite effect was observed in 2, 2, and 2 patients, respectively. There was no statistically significant mean effect of ETS on airway responsiveness during night; however, there was significant heterogeneity in individual responses (P = 0.0002). Patients with and without a history of ETS-induced symptoms did not show different responses to experimental ETS exposure. In conclusion, our data suggest that in single adult subjects with mild asthma, acute exposure to ETS in the evening can produce a deterioration of airway tone and responsiveness during the night, with wide interindividual variability in the response.
Adult↗
Effects of a single saturation dive on lung function and exercise performance.
We studied the effects of an experimental saturation dive to 360 and 450 m in a simulation chamber on spirometric lung function, diffusing capacity, pulmonary compliance, and exercise performance in eight professional divers (age 22-40 years). To assess intraindividual variability, all parameters were measured on 2 days before and on 2 consecutive days immediately after the dive. For the group as a whole there was a significant increase in vital capacity and alveolar volume, and a decrease in Krogh factor and specific compliance (P < 0.01). These changes were reduced on the 2nd day after the dive. All subjects showed lowered exercise performance after the dive. Arterial pressure of oxygen and ventilation during exercise increased (P < 0.01), whereas arterial pressure of carbon dioxide, oxygen uptake, and anaerobic threshold decreased (P < 0.01). Exercise parameters showed only a slight trend towards pre-dive values on the 2nd day after a dive. The individual analysis revealed that after the dive two subjects showed a marked decrease in diffusing capacity and a more than average decrease in Krogh factor (TLCO/VA). One of them had signs of mild decompression sickness and the other, signs of pre-existing obstructive airways disease. Our data are compatible with the hypothesis that the effects of a single deep saturation dive on pulmonary function and exercise performance are the results of counteracting mechanisms. We suggest that lung volumes increase due to the enhanced work of breathing during a deep saturation dive and that these changes could mask an impairment in gas exchange. Furthermore, a saturation dive can induce an apparent deterioration of pulmonary function.
Adult↗
Effect of 3 hours of passive smoke exposure in the evening on inflammatory markers in bronchoalveolar and nasal lavage fluid in subjects with mild asthma.
OBJECTIVE: The aim of this study was to investigate the effect of environmental tobacco smoke (ETS) exposure in the evening on inflammatory changes in bronchoalveolar (BAL) and nasal lavage (NAL) fluid. METHODS: Ten subjects with mild asthma [mean (+/- SD) age, 25 +/- 2 years, FEV1% pred., 93 +/- 6%, PC20FEV1 0.44 x 5.11 mg/ml methacholine] were exposed to ETS (22.4 +/- 1.2 ppm CO) or ambient air (sham) for 3 h (7.00 to 10.00 p.m). Bronchoscopy was performed the following morning at 7.00 a.m. A visual endoscopic score was assessed, and BAL fluids were analyzed for cellular composition and concentrations of histamine, albumin, eosinophilic cationic protein, myeloperoxidase, hyaluronic acid, tryptase, prostanoids and leukotrienes. Nasal lavages were performed 30 min prior to and 30 min after exposures, and NAL fluids were analyzed for histamine, albumin, eosinophilic cationic protein, myeloperoxidase, hyaluronic acid, and tryptase. RESULTS: There was a significant rise in symptoms after ETS exposure compared with sham (P < 0.05). Spirometric lung function did not change during or after exposure compared with pre-session values. Visual bronchoscopic scoring revealed no significant effect of ETS exposure, nor did BAL cells and mediators or NAL mediators as compared with pre-challenge or post-sham values. CONCLUSION: In the subjects tested, a 3-h ETS exposure in the evening appeared not to have an inflammatory effect detectable in BAL or NAL fluid.
Adult↗
Inherent tone of human bronchus: role of eicosanoids and the epithelium.
1. Airway preparations of different species possess varying degrees of inherent tone which is the result of different metabolites of arachidonic acid in different species. In human bronchial smooth muscle in vitro we have investigated the effects of 5-lipoxygenase inhibition (zileuton, 10 microM), cyclo-oxygenase inhibition (indomethacin, 1 microM) and mechanical epithelium removal on inherent tone. The shunting of arachidonic acid by inhibition of one or other of these enzymes, as a possible explanation for the effects observed, has also been investigated. 2. Zileuton caused a significant fall in tone either alone (-107 +/- 33 mg) or after cyclo-oxygenase inhibition (-203 +/- 48 mg) and this effect was not significantly altered by epithelial removal (-191 +/- 43 mg alone; -333 +/- 88 mg after indomethacin). Indomethacin increased tone when applied alone (160 +/- 94 mg), but this effect only reached statistical significance after 5-lipoxygenase inhibition, (210+/-81 mg; P<0.05). Epithelial removal did not alter the effect of indomethacin when applied alone (213+/-97 mg), but significantly reduced the effect of indomethacin after 5-lipoxygenase inhibition (34 +/- 23 mg; P<0.05). 3. These data suggest that inherent tone in human bronchus is largely the result of contractile 5-lipoxygenase products. However, the involvement of cyclo-oxygenase products cannot entirely be discounted, since in the presence of 5-lipoxygenase inhibition contractile and relaxant eicosanoids originating from the bronchial epithelium appear to influence significantly inherent tone.
Adult↗
Augmentation of human neutrophil and alveolar macrophage LTB4 production by N-acetylcysteine: role of hydrogen peroxide.
1. The actions of N-acetylcysteine (NAC) on hydrogen peroxide (H2O2) and leukotriene B4 (LTB4) production by human resting and stimulated peripheral blood neutrophils and alveolar macrophages were investigated. 2. At a concentration of 100 microM, NAC significantly (P < 0.01) suppressed the accumulation of H2O2 in the incubation medium of resting and opsonized zymosan (OZ; 0.5 mg ml[-1])- or N-formylmethionyl-leucyl-phenylalanine (fMLP; 1 microM)-stimulated neutrophils and of resting and OZ-stimulated macrophages. At concentrations of 10 microM and above, NAC augmented significantly the level of LTB4 in the supernatants of OZ- and fMLP-stimulated neutrophils (P < 0.01 and P < 0.05, respectively) and OZ-stimulated macrophages (P < 0.05 at 10 microM, P < 0.01 at 100 microM NAC). 3. NAC (100 microM) caused a significant (P < 0.01) reduction in the quantity of measurable H2O2 when incubated with exogenous H2O2 concentrations equivalent to those released from OZ-stimulated neutrophils and macrophages. At no concentration did NAC affect quantitites of measurable LTB4 when incubated with exogenous LTB4. 4. Superoxide dismutase (SOD), which catalyzes the conversion of superoxide anion to H2O2 had no significant effect on LTB4 production by human neutrophils. In contrast, catalase, which catalyzes the conversion of H2O2 to H2O and O2, caused a pronounced, statistically significant (P < 0.01) increase in the levels of LTB4 measured in the supernatants of OZ- and fMLP-stimulated neutrophils. 5. H2O2 (12.5 microM and 25 microM, concentrations equivalent to those measured in the supernatants of activated neutrophils and alveolar macrophages, respectively) caused a small (13%) decrease in the quantity of measurable LTB4 (P = 0.051 and P < 0.05 at 12.5 microM and 25 microM, respectively) that was inhibited by NAC (100 microM) but not by catalase (400 u ml[-1]). 6. In conclusion, the anti-oxidant drug, NAC, increases LTB4 production by human neutrophils and alveolar macrophages, probably through the elimination of cell-derived H2O2. LTB4 undergoes a H2O2-dependent oxidation that is inhibited by NAC but this is unlikely to account fully for the increased levels of LTB4, suggesting that NAC may increase LTB4 production by blocking the H2O2-dependent inhibition of a synthetic enzyme, such as 5-lipoxygenase.
Acetylcysteine↗
Conservation of bronchiolar wall area during constriction and dilation of human airways.
We assessed the effect of smooth muscle contraction and relaxation on airway lumen subtended by the internal perimeter (Ai) and total cross-sectional area (Ao) of human bronchial explants in the absence of the potential lung tethering forces of alveolar tissue to test the hypothesis that bronchoconstriction results in a comparable change of Ai and Ao. Luminal area (i.e., Ai) and Ao were measured by using computerized videomicrometry, and bronchial wall area was calculated accordingly. Images on videotape were captured; areas were outlined, and data were expressed as internal pixel number by using imaging software. Bronchial rings were dissected in 1.0- to 1.5-mm sections from macroscopically unaffected areas of lungs from patients undergoing resection for carcinoma, placed in microplate wells containing buffered saline, and allowed to equilibrate for 1 h. Baseline, Ao [5.21 +/- 0.354 (SE) mm2], and Ai (0.604 +/- 0.057 mm2) were measured before contraction of the airway smooth muscle (ASM) with carbachol. Mean Ai narrowed by 0.257 +/- 0.052 mm2 in response to 10 microM carbachol (P = 0.001 vs. baseline). Similarly, Ao narrowed by 0.272 +/- 0.110 mm2 in response to carbachol (P = 0.038 vs. baseline; P = 0.849 vs. change in Ai). Similar parallel changes in cross-sectional area for Ai and Ao were observed for relaxation of ASM from inherent tone of other bronchial rings in response to 10 microM isoproterenol. We demonstrate a unique characteristic of human ASM; i.e., both luminal and total cross-sectional area of human airways change similarly on contraction and relaxation in vitro, resulting in a conservation of bronchiolar wall area with bronchoconstriction and dilation.
Bronchi↗
Passive sensitization of human airways induces myogenic contractile responses in vitro.
We assessed effects of passive sensitization on human bronchial smooth muscle (BSM) response to mechanical stretching in vitro. Bronchial rings were sham (control) or passively sensitized overnight by using sera from donors demonstrating sensitivity to Dermatophagoides farinae and having immunoglobulin E (IgE) concentrations of 2,600 +/- 200 U/ml. Tissues were fixed isometrically to force transducers to measure responses to electrical field stimulation (EFS) and quick stretch (QS). The myogenic response to QS was normalized to the maximal response to EFS (%EFS). The myogenic response of sensitized BSM was 47.9 +/- 10.9 %EFS to a QS of approximately 6.5% optimal length (Lo); sham-sensitized tissues had a myogenic response of 13.5 +/- 6.4 %EFS (P = 0.012 vs. passively sensitized). A QS of approximately 13% Lo in sensitized BSM caused a response of 82.8 +/- 20.9 %EFS; sham-sensitized tissues developed a response of 38.2 +/- 17.3 %EFS (P = 0.004). BSM incubated with serum from nonallergic donors did not demonstrate increased QS response (4.6 +/- 1.4 %EFS, P = not significant vs. tissue exposed to atopic sera). However, tissues incubated in sera from nonatopic donors supplemented with hapten-specific chimeric IgE (JW8) demonstrated augmented myogenic response to QS of approximately 6.5% Lo (21.9 +/- 6.2 %EFS, P = 0. 027 vs. nonatopic sera alone). We demonstrate that passive sensitization of human BSM preparations causes induction and augmentation of myogenic contractions to QS; this hyperresponsiveness corresponds to the IgE concentration in sensitizing sera.
Allergens↗
Role of IgE in hyperresponsiveness induced by passive sensitization of human airways.
Incubation of airways from nonatopic patients with serum from patients with high IgE levels confers responsiveness to "specific" (allergen) and hyperresponsiveness to "nonspecific" (histamine) stimuli. We have tested the hypothesis that the level of IgE determines the degree of specific and nonspecific responsiveness. Bronchial rings from nonatopic patients were sensitized overnight with serum containing high levels of allergen-specific IgE, or with an allergen-specific chimeric IgE (JW8) in physiologic buffer. In vitro responsiveness to allergen and histamine was evaluated and compared with non-sensitized tissues from the same patients. Responses to specific allergen were demonstrated in all tissues sensitized with atopic serum or chimeric IgE, but not in nonsensitized tissues. Allergen responses were specific, since tissues sensitized using serum containing high Dermatohagoides farinae-specific IgE only, did not respond to either horse or dog allergens. The potency and magnitude of the maximal contraction to histamine was significantly (p < 0.05) increased in tissues sensitized using atopic serum with high total IgE concentrations compared with nonsensitized preparations, but was unchanged in tissues sensitized using chimeric IgE or serum with low total IgE levels. Therefore, specific IgE determines allergen responsiveness in passively sensitized human airways, but histamine hyperresponsiveness is independent of specific IgE and appears to be related to some other factor associated with serum containing high concentrations of total IgE.
Aged↗
Airway responsiveness to sulfur dioxide in an adult population sample.
We determined the prevalence of airway hyperresponsiveness to sulfur dioxide (SO2) in an adult population sample of 790 subjects 20 to 44 yr of age. Subjects were drawn randomly from the population of Hamburg, Northern Germany, within the framework of the European Community Respiratory Health Survey. In addition, we analyzed the relationship between SO2 responsiveness and a number of risk factors, such as a history of respiratory symptoms, methacholine responsiveness, and atopy derived from skin-prick test results. SO2 inhalation challenges were performed during isocapnic hyperventilation at constant rate (40 L x min(-1), for 3 min) with doubling concentrations of SO2 up to a maximum concentration of 2.0 ppm. If subjects achieved a 20% decrease in FEV1 from baseline during the challenge, they were considered to be hyperresponsive to SO2. The raw prevalence of SO2 hyperresponsiveness within the population sample studied was 3.4% (95% confidence interval [CI]: 2.3 to 5.0%). Adjustment for nonparticipation led to an estimated prevalence of SO2 hyperresponsiveness of 5.4%. Among subjects with hyperresponsiveness to methacholine, 22.4% (95% CI: 20.1 to 25.3) demonstrated hyperresponsiveness to SO2. There was no significant correlation between the degrees of hyperresponsiveness to methacholine and SO2. Predictors of a positive SO2 response were hyperresponsiveness to methacholine (p < 0.0001), a positive history of respiratory symptoms (p < 0.05), and a positive skin-prick test to at least one common allergen (p < 0.05). We conclude from these data that airway hyperresponsiveness to SO2 can be found in about 20 to 25% of subjects within the 20- to 44-yr age range who are hyperresponsive to methacholine.
Adult↗
A short protocol for methacholine provocation testing adapted to the Rosenthal-Chai dosimeter technique.
BACKGROUND: The purpose of this study was to develop a rapid and safe methacholine provocation protocol equivalent to the standard dosimeter technique. METHODS: The rapid protocol comprised a short and a long subprotocol. The challenge was started with one of these subprotocols according to the subject's answers to a questionnaire and baseline lung function. If FEV1 dropped by 10% during the short subprotocol, the test was continued with the long subprotocol. The concentrations of methacholine and numbers of inhalations were chosen to match the concentrations of the standard method as closely as possible. To verify the protocol, we compared both methods in 38 subjects with asthma and 10 control subjects. RESULTS: The provocative concentrations of methacholine (PC20FEV1) obtained with the standard method and the rapid method were within one doubling concentration in 38 of 40 subjects. None of the subjects who were normoreactive according to the standard method (PC20FEV1 > 8 mg/mL) responded in the rapid protocol. The standard method required, on average (+/-SD), 34+/-11 min; the rapid method required 15+/-3 min. CONCLUSIONS: The rapid provocation protocol is equivalent to the standard method, without loss in precision and safety, but with considerable saving in time. Therefore, it appears to be particularly suited for studies that require comparability with provocative concentrations obtained with the Rosenthal-Chai dosimeter method.
Adult↗
[Indications and performance of a 6 minute treadmill test in pneumology].
The aim of rehabilitative measures for chronic airway and lung diseases is the restoration or improvement of disturbed lung function along with increased quality of life. The six minute walking-distance test (6 min WDT) is a suitable method for the assessment of the physical fitness of patients with chronic pulmonary diseases. The results of the 6 min WDT do not correlate strictly with lung function but correlate rather better with quality of life parameters and dyspnoea ratings; they therefore provide a better reflection of the patient's condition in daily life than is given by lung function measurements. Such a parameter may be appropriate in considerations of the potential for rehabilitation, in addition to its usefulness in questions of assessment.
Exercise Test↗
[Theophylline and selective phosphodiesterase inhibitor in therapy of obstructive respiratory tract diseases].
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Bronchodilator Agents↗
[Comparison of nasal and bronchial production of nitric oxide in healthy probands and patients with asthma].
Nitric oxide (NO) appears to play an important role in the pathophysiology of airway diseases as suggested from measurements of NO in exhaled air, animal and in vitro experiments. As NO is produced in variable amounts within the bronchial system and the nose, we studied the relationship between nasal and bronchial production of NO in patients with asthma and determined to which extent these productions were increased compared to healthy subjects. The nasal and bronchial production rates of NO as a function of breathholding time were assessed in 10 healthy subjects, 7 patients with asthma without inhaled corticosteroids, and 5 patients with asthma and a therapy of inhaled corticosteroids. After a breathhold of 10 s bronchial NO concentrations were elevated in the patients with asthma without steroids by the factor 3.5 (p < 0.005) and nasal concentrations by the factor 1.2 (n.s.) compared to healthy subjects. NO concentrations increased with time. Correspondingly, bronchial production rates were increased by factor 2.7 (p < 0.01) and nasal production rates by factor 1.1 (n.s.) in asthmatic compared to healthy subjects. The asthmatic patients with steroids showed lower production rates than those without steroids. We conclude from these data that in patients with asthma as compared to normal subjects bronchial production of NO is markedly increased, whereas the corresponding relative increase in nasal production is lower.
Adult↗