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In order to study changes in respiratory sounds associated with acute bronchoconstriction and -dilatation, breath sounds of 11 children with asthma (age range, 10–14 years) were recorded at the chest and at the trachea during histamine challenge test and after subsequent bronchodilatation. The changes in frequency spectra of breath sounds were compared with simultaneous changes in forced expiratory volume in 1 second (FEV1). In seven children who responded to histamine with a decrease in FEV, of more than 15%, there was a significant relationship between percentage change in FEV1 (ΔFEV1) and percentage change in median frequency (ΔF50) of expiratory breath sounds recorded at the chest (r = 0.865; β = −0.706, P = 0.0001) and at the trachea (r = 0.888; β = 1.12, P = 0.0001). The association between breath sound intensity and FEV1 was weaker. Based on ANOVA, the increase of F50 during the challenge test was significantly larger in children who responded to histamine than in those who were non-responsive (P = 0.0016). At the chest, a decrease of 15% in FEV1 corresponded to an increase of 8% in expiratory F50. The provocative dose of histamine inducing a decrease of 15% in FEV1 (PD15FEV1) and the provocative dose causing an increase of 8% in F50 (PD8F50) were significantly related (r = 0.927, P = 0.003). We conclude that spectral analysis of breath sounds can be used to indicate airway obstruction during bronchial challenge tests in children, and may be adapted for tests in pre-school children. The results suggest that the same mechanisms that induce airflow limitation due to inhaled histamine may generate an increase in frequency content of breath sounds in children with asthma.Pediatr Pulmonol. 1994;18:170–177. © 1994 Wiley-Liss, Inc.

The preventive effects of inhaled formoterol (a new beta 2-agonist) and salbutamol aerosols on histamine-induced bronchoconstriction were studied in 12 patients with mild or moderate asthma in a placebo-controlled, double-blind study. Three hours after the administration of 12 micrograms formoterol, 200 micrograms salbutamol (doses with equal bronchodilator effects) or placebo via aerosol, histamine challenge was undertaken, using a dosimetric jet nebulizer with controlled tidal breathing. The noncumulative dose of histamine diphosphate aerosol provoking a 15% fall in FEV1 (PD15) was calculated. The PD15 after inhalation of 12 micrograms formoterol was significantly higher than that after 200 micrograms salbutamol (median values 640 and 310 micrograms, respectively; p < 0.01). For both treatments, the PD15 was significantly higher than that after placebo (median 185 micrograms). The results indicate that the preventive effect against histamine-induced bronchoconstriction at 3 h after drug is significantly better with formoterol than with salbutamol when using inhaled doses with an equal acute bronchodilator effect.

The presence of airway inflammation even in mild asthma points to the potential value of antiinflammatory therapy. We compared the effect of an inhaled corticosteroid, budesonide, with that of an inhaled beta 2-agonist, terbutaline, in the long-term treatment of newly detected asthma.We studied 103 patients (29 male and 74 female patients 15 to 64 years old) in whom asthma had appeared within the previous year. The patients were randomly assigned in blinded fashion to two treatment groups: one to receive 600 micrograms of inhaled budesonide twice a day, and the other to receive 375 micrograms of inhaled terbutaline twice a day. The study period was two years.After six weeks of treatment, the patients treated with budesonide tolerated inhaled histamine better than the patients treated with terbutaline (a difference of one doubling dose step, P less than 0.001), and the difference was sustained. Patients' diaries kept during the first three months of the study and during the last month of the first and second years showed budesonide to be more effective than terbutaline in improving peak expiratory flow in the morning (average increase from the pretreatment value, 32.8 liters per minute for budesonide vs. 4.8 liters per minute for terbutaline; P less than 0.001) and in the evening (P less than 0.01). Budesonide was also more effective in reducing the symptoms of asthma (P less than 0.01) and the use of supplemental beta 2-agonist medication (P less than 0.01). Ten patients were withdrawn from the terbutaline group because treatment was insufficiently effective, whereas only one dropped out of the budesonide group. The adverse reactions to both treatments were few and mild.Antiinflammatory therapy with inhaled budesonide is an effective first-line treatment for patients with newly detected, mild asthma, and it is superior to the use of terbutaline in such patients.

The effect of beta-adrenoceptor antagonists, with and without intrinsic sympathomimetic activity, on the regulation of lymphocytic beta adrenoceptors during acute physical exercise was studied. Seven healthy volunteers underwent a graded maximal ergometer test after treatment for 7 days with placebo, propranolol (2 x 80 mg/day), or pindolol (2 x 10 mg/day). Each subject received the three types of drug treatment in a double-blind, randomized fashion, with 3 weeks wash-out periods between the on-drug periods. The mean resting density of lymphocytic beta adrenoceptors was 46 +/- 5 fmol/mg protein (mean +/- SEM) during placebo, 53 +/- 5 fmol/mg protein during propranolol, and 29 +/- 4 fmol/mg protein during pindolol treatment (p less than 0.05, pindolol vs. propranolol). Exercise induced a significant up-regulation of the beta-adrenoceptor density during each treatment modality, but the increment was attenuated during propranolol (mean elevation, 16 +/- 2 fmol/mg protein, p less than 0.05) and pindolol intake (13 +/- 4 fmol/mg protein, p less than 0.02) as compared with the placebo value (56 +/- 13 fmol/mg protein). Moreover, exercise-induced increment of lymphocytic cyclic AMP (cAMP) production was virtually abolished by the two beta-adrenoceptor antagonists. In conclusion, administration of beta-adrenoceptor antagonists is associated with a subnormal up-regulation of the lymphocytic beta-adrenoceptors and alterations in their functioning during heavy physical effort. This attenuation is not modified by intrinsic sympathomimetic activity of the compound.

Nine adult asthmatics with a history of nocturnal symptoms and with morning dips in peak expiratory flow (PEF) were treated for 10-14 days with 24-h controlled-release preparation of theophylline (Th), or a controlled-release preparation of terbutaline (Te), in a double-blind cross-over experiment. During treatment with 450-900 mg Th in the evening morning, plasma drug levels ranged from 53-95 (mean 73) mumol/l. The Te dose was 7.5 mg twice daily. Morning PEF values during Th (mean 338 l.min-1) and Te (316 l.min-1) were not significantly different. There were no significant differences between the treatments in average nocturnal oximetric O2 saturation (91.9% during Th and 91.0% during Te), or the amount of nocturnal body movement, recorded with a static charge sensitive bed (total number of movements 146 during Th and 120 during Te). No difference between the treatments was seen with respect to assessment by the subjects of sleep quality, which was considered fair or good. The findings suggest that in moderately severe asthma, nocturnal oxygenation and sleep quality were similar during the two treatments.

Premature birth is related to a chronic respiratory morbidity, which may persist until school-age. In these children, the forced oscillation technique would be suitable for evaluation of lung function even at preschool age, since it requires only minimal patient cooperation. In order to investigate the oscillometric findings related to premature birth, using the oscillation technique and conventional lung function methods 49 school-aged children born prematurely with (n=15) or without (n=34) chronic lung disease (CLD), and 18 healthy children born at full term were studied. Children with CLD had higher respiratory resistance (Rrs,5) and lower reactance (Xrs,5) than prematurely born children without CLD or healthy controls. Both Rrs,5 (r=-0.55, p

The Comparison of Inhaled Bronchodilators by Lung Sound Analysis in Children with Acute Bronchiolitis

Summary Three cases of severe laryngeal papillomatosis beginning in early childhood are presented. Several methods of treatment were tried, but lasting results were achieved by suction diathermy. The laryngeal lumen was totally obliterated in all cases during the course of the disease. The patients were successfully operated on by making a laryngofissure in the front part of the larynx, excising the scar and enlarging the lumen by a median incision in the back wall of the larynx. An indwelling prosthesis was placed in the larynx for several months. After removing the prosthesis, the laryngeal lumen was dilated several times by oesophageal sounds. All patients were successfully decannulated. The results of treatment are evaluated both clinically and by ventilatory function studies. Central airway obstruction persisted in two cases.

Summary In an industrial community, Linnavuori, (population 1000) over 100 people developed fever, cough, and dyspnoea 3 to 6 hours after sauna or bathing. This epidemic began in August of 1978 and ended gradually in December. The water source of the community was a small (0.4 km2) lake; in November it was found that the water was contaminated with several bacteria, fungi, and algae. Precipitating antibodies to these bacterial and fungal antigens were not found in the sera of symptomatic patients. To show that tap water, purified by the local waterworks, had provoked the symptoms, four clinically typical patients were each twice challenged. Two of the patients visited their usual public sauna, the two others took a bath at home. Two patients inhaled home tap water aerosol, one inhaled lake water vapor and one home tap water vapor in hospital. Three to six hours after seven of the eight challenges the patients showed two or more of the following symptoms and signs: chills, fever, dry cough, dyspnoea, and inspiratory crepitant râles. Six provocations increased the amount of segmented neutrophils and in each case the lung diffusion capacity decreased significantly. Although the clinical picture resembles extrinsic allergic alveolitis, it is possible that bacterial endotoxins have induced alternative pathway complement activation and release of leukocyte pyrogens. A respiratory syndrome much resembling exogenous allergic alveolitis, and caused by micro-organism-contaminated water from air humidifiers and ventilation systems, has become more commonly diagnosed in the 1970's. This disease is also called hypersensitivity pneumonitis or humidifier fever. Banaszak, Thiede & Fink (1970) described four office clerks whose symptoms were shown to be caused by contamination of the office ventilation system by a thermophilic actinomycete. Inhalation tests with the homologous antigen provoked similar symptoms. Fink et al. (1971) found

Rosenlof K, Gronhagen-Riska C, Sovijarvi A, Honkanen E, Tikkanen I, Ekstrand A, Piirila P, Fyhrquist F (IV Department of Internal Medicine, and Department of Pulmonary Medicine. Helsinki University Central Hospital. Finland). Beneficial effects of erythropoietin on haematological parameters, aerobic capacity and body fluid composition in patients on haemodialysis. Eleven patients on haemodialysis were treated with erythropoietin (EPO). 50–200 U kg−1 once to three times a week, for up to 1 year. After outset of EPO all patients became transfusion-independent. Four patients did not reach the target haemoglobin (Hb) level 100 gl−1 in 5 months. These patients had higher serum concentrations of aluminium (225 ± 87 μgl−1, mean ± SD) than the responding patients (55 ± 56 μgl−1). Addition of desferrioxamine to treatment with EPO resulted in a rapid rise in Hb values in these patients. Thus, aluminium may inhibit EPO responsiveness. All patients were iron overloaded. Serum ferritin levels declined in all but one patient with secondary haemochromatosis. In exercise tests the aerobic capacity and oxygen uptake increased during EPO therapy. Peak oxygen consumption (Vo2 peak), oxygen pulse, oxygen uptake at anaerobic threshold (AT) and total work output (W max) increased 19%, 36%, 26% and 24%, respectively. Lean body mass (LBM) increased by 8%. Taken together, all clinical EPO effects measured appeared clinically favourable.

Summary. Arterial blood gases were analysed from eight patients with clinically typical hyperventilation syndrome (HVS^ and with no signs of organic diseases, and from eight control patients with no cardiopulmonary or metabolic disease; the blood samples were drawn at rest, during an orthostatic test and during and 10 min after maximal exercise. In all stages of the tests the arterial oxygen tension of the HVS patients was at a high normal level. By the end of the orthostatic test, during maximal exercise and 10 min after the exercise every HVS patient had moderate to marked hypocapnia. At every stage of the tests the arterial Pco2 of the HVS patients was significantly lower than that of the control patients; during standing and after exercise the arterial pH was significantly higher in the HVS group than in the control group. Either during the orthostatic test or 10 min after the exercise or at both situations all of the HVS patients, but none of the controls, showed respiratory alkalosis. The results indicate that standing up and heavy exercise can markedly stimulate the HVS patients to hyperventilate. Thus, orthostatic and exercise tests combined with blood gas analyses seem to be useful in diagnosing the HVS.

The effects on lung tissue and tumor of natural human alpha interferon (IFN) and radiotherapy were investigated in a multimodality treatment program for selected patients with small cell carcinoma of the lung (SCLC). Interferon was given first as a single agent, then concomitantly with radiotherapy to 12 previously untreated patients with limited disease. At disease progression outside the chest, interferon was discontinued and combination chemotherapy was initiated. In the first series, 7 patients received a high interferon induction dose (800 X 10(6) IU i.v. over 5 days) followed by low-dose maintenance therapy (6 X 10(6) IU i.m. TIW), median total dose 1380 X 10(6) IU (range 794-2074). At local progression, split-course radiotherapy, 55 Gy/20 F/7 wk, was added to interferon therapy. In the second series, 5 patients received low-dose interferon from the start (6 X 10(6) IU i.m. daily) combined with twice-a-day fractionated radiotherapy 44 Gy/40 F/4 wk. Median total dose of interferon in this series was 698 X 10(6) IU (range 354-828). Tumor response and normal tissue reactions were evaluated by monthly chest X rays, 3-monthly CT scans, restaging bronchoscopies and by serial respiratory function tests. Autopsy specimens from both lungs within and outside the radiation field were systematically evaluated when available. After the completion of radiotherapy, there were 4/7 CR in the high-dose IFN group compared to 3/5 CR in the low-dose IFN group. Rapid shrinkage of huge tumor masses was observed. At 2 months post radiotherapy radiological grade III fibrosis occurred in 4/7 patients in the high-dose and 1/5 patients in the low-dose group. Lung function studies showed a significant decrease in diffusing capacity and in lung volumes. Seven patients died within 12 months from start of interferon treatment, one of them from treatment complication. At autopsy the tumor area was in most cases replaced by severe fibrosis. Outside the radiation field lung fibrosis was mild. Our results suggest enhancement of radiation effect by interferon with a possible dose and/or schedule dependence of interferon and radiotherapy and call for more clinical studies of IFN and radiotherapy in combination.

From 1970 to 1988, 9 patients were treated for tracheobronchial rupture arising from nonpenetrating thoracic trauma. All patients the dyspnea and pneumothorax. Four patients had rupture of inc right main bronchus, 3 had rupture of the left main bronchus, 1 had rupture of the right intermediate bronchus, and 1 had rupture of the trachea. Four patients were operated on within 24 hours. Three of them had a massive air leak into the suction drainage and underwent thoracotomy. The fourth patient presented difficulties with endotracheal intubation and required a collar incision. Primary reconstruction was performed in all 4 patients. Five patients had a delay of nine to 89 days before operation. All of them had good primary healing but later developed dyspnea. Bronchoscopy revealed scar obstruction in all S. The stenosed segment was resected in 4 patients at thoracotomy. The fifth patient, who had an intermediate bronchus rupture, underwent lobectomy. Seven patients were followed from 6 months to 18 years. One of them, who had a nine-day delay in treatment, needed further operation 6 months after the accident because of scar obstruction. The other 6 patient were interviewed, examined, and studied with spirometry, body pelythysmography, bronchoscopy, and bronchography. In these 6 patients no stricture was seen, and there was no reduced pulmonary function due to the rupture even when operation was delayed.

Non-ventilated lung volume (trapped air) during tidal breathing and several other lung function parameters were determined in 19 patients with extrinsic allergic alveolitis, most of them with farmer's lung, and in 28 non-smoking healthy subjects. The trapped air was significantly larger (p0.01) in the patients (mean 0.73 litres) than in normal subjects (mean 0.32 litres); in 7 patients (37%) it was definitely enlarged. The results suggest that the frequent increase of trapped air may be caused by patchy small airways occlusion due to bronchiolitis.

The neural mechanisms involved in the detection of natural complex sounds were studied by recording single-neuron responses from 132 cells in the primary auditory cortex of the cat. The cats were paralyzed and under neuroleptanalgesia (NLA). The cells were first stimulated with pure tones; the responses were then compared with those evoked by many different types of complex sounds, most of which were animal vocalizations. Per-stimulus-time (PST) histograms constructed from the responses to repetitive stimuli were compared with the corresponding sound spectrograms formed from the sounds used as stimuli. Of 100 cells 68 per cent gave predictable responses to complex sounds on the basis of their responses to different pure tone frequencies. In 32 per cent of the cells the responses were unpredictable. Half of these cells did not react to pure tones at all but responded to one or more animal vocalizations or generator sounds with different patterns. Some cells reacted to pure tones in quite a different way than to certain complex sounds, e.g. with inhibition instead of excitation. These results indicate that cells in the primary auditory cortex of the cat reacting in an unpredictable way to sounds with a complex structure have a more or less specialized function, in detecting and analyzing natural and other complex sound patterns. Cells reacting phasically to pure tones seem to be involved in the detection of transient sound elements.

Information about the effects of neuroleptanalgesia (NLA) on the electrical function of the auditory cortex was obtained by recording gross electrical and unit activity in the primary auditory cortex of the cat after administration of droperidol and fentanyl (Thalamonal). In the EEG no change could be detected visually after an intramuscular injection of Thalamonal, nor did spectral analyses reveal any significant alteration. Pentobarbital, on the other hand, caused a highly significant slowing of the EEG. Single-cell activity was clearly depressed by pentobarbital, but during NLA most of the functional neurons of the auditory cortex were firing spontaneously and responded readily to various types of sound stimuli. From these findings the authors conclude that NLA at the level of surgical anesthesia does not significantly affect the electrical function of the auditory cortex and the auditory pathway in the cat.

The determination of human blood acetaldehyde (AcH) concentrations is complicated by two artefactual reactions, one resulting in the disappearance of AcH prior to deproteinization of the blood and the other resulting in the formation of AcH during deproteinization. The AcH formation increases with increasing ethanol concentration and decreases with increasing blood dilution, while the rapid AcH disappearance is initiated at the start of the blood collection. The magnitudes of these artefactual reactions are of such an order that a re-evaluation of previous reports on human blood AcH levels is needed. To circumvent these difficulties we suggest that blood should be deproteinized immediately (

This study was undertaken to estimate the accuracy of 133-xenon radiospirometry for determination of FRC in healthy subjects. Forty healthy volunteers, both smokers and non-smokers, were examined. The FRC of each subject was concurrently determined with radiospirometric, He-dilution in closed circuit, and body plethysmographic methods. The radiospirometric and He-dilution measurements were done in supine and in sitting positions, the body plethysmography on sitting subjects, only. The mean FRC measured by radiospirometry (FRCRS) was 0.72 1 larger than that measured by helium spirometry (FRCHe) in sitting position (P0.01). In supine position the FRCRS was 0.65 1 larger than the FRCHe (P0.01). The body plethysmography gave FRC (TGV) 0.35 1 larger than the FRCHe sitting (P0.01). The FRCHe and the FRCRS in the sitting position were 0.48 and 0.55 1 larger than in the supine position (P0.01), respectively. Trapped air correlated significantly (P0.01) with the difference FRCRS-FRCHe, when sitting. The results indicate that the FRC determined radiospirometrically is significantly larger than the FRC determined with He-spirometry. The difference is systematic, suggesting that it is caused by 133-xenon dissolved in blood and accumulated in tissues of the thoracic cage and by dissimilar representation of trapped air in FRCRS and FRCHe. With eventual correction of the systematic error, the FRC obtained as a by-product of radiospirometry may be used, e.g. for clinical purposes.

We have investigated the effect of acute and long-term bronchodilator treatment on the distribution of ventilation and perfusion in 15 asthmatics using a gamma camera, krypton-81m (for ventilation) and technetium-99m macroaggregate (for perfusion). Individual peak expiratory flow (PEF) values before bronchodilation were slightly or moderately below the predicted values. The simultaneous ventilation images (analysed visually) showed areas of delayed ventilation in all patients (mean distribution score on 3-point scale 2.1). After isoprenaline inhalation (240 micrograms) the mean PEF increased by 24%, but the distribution of ventilation remained virtually unchanged in all patients (mean score 2.0). Simultaneously defects in perfusion could be seen in all patients (mean score 1.5). After intensive treatment, when the mean PEF increased by a further 29%, the distribution scores of ventilation and perfusion fell to 0.8 and 0.9, respectively. The results indicate that, without intensive and long-term treatment, appreciable inequality of ventilation and perfusion are usual consequences of asthma; and suggest that although larger airways are dilated by isoprenaline inhalations residual bronchial obstruction may still remain in some smaller airways, maintaining uneven distribution. Perfusion disturbances seem to be secondary to changes in regional ventilation.

Reliable long-term assessment of cough is necessary in many clinical and scientific settings. A new method for long-term recording and automatic analysis of cough is presented. The method is based on simultaneous recording of two independent signals: high-pass filtered cough sounds and cough-induced fast movements of the body. The acoustic signals are recorded with a dynamic microphone in the acoustic focus of a glass fiber paraboloid mirror. Body movements are recorded with a static charge-sensitive bed located under an ordinary plastic foam mattress. The patient can be studied lying or sitting with no transducers or electrodes attached. A microcomputer is used for sampling of signals, detection of cough, statistical analyses, and on-line printing of results. The method was validated in seven adult patients with a total of 809 spontaneous cough events, using clinical observation as a reference. The sensitivity of the method to detect cough was 99.0 percent, and the positive predictivity was 98.1 percent. The system ignored speaking and snoring. The method provides a convenient means of reliable long-term follow-up of cough in clinical work and research.

In congestive heart failure (CHF), prolonged exposure to high plasma catecholamine levels may reduce the responsiveness of the adrenergic system to physiologic stimuli. In healthy subjects, exercise is known to induce a rapid up-regulation of lymphocytic beta adrenoceptors. Lymphocytic beta-adrenoceptor density, lymphocytic basal and isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) response, plasma catecholamine concentrations and plasma cAMP levels were studied during maximal ergometer exercise in 11 patients with CHF secondary to dilated cardiomyopathy and in 6 healthy control subjects. At rest, there was no difference in the lymphocytic beta-adrenoceptor levels between the patients and control subjects (48 +/- 3 vs 42 +/- 5 fmol/mg protein, respectively). However, the exercise-induced increase in lymphocytic beta adrenoceptors was attenuated in patients when compared with controls (26 +/- 6 fmol/mg protein [56%] vs 75 +/- 16 fmol/mg protein [204%], respectively, p less than 0.02). A subgroup of 4 patients with the lowest exercise capacity (peak oxygen uptake less than 12.5 ml/min/kg) had even more reduced up-regulation compared with the other 7 patients (13 +/- 1 fmol/mg protein [29%] vs 34 +/- 9 fmol/mg protein [71%], p less than 0.05). The lymphocytic cAMP response at rest and during exercise tended to be lower in patients compared with controls, but the differences did not reach statistical significance. The plasma levels of epinephrine and norepinephrine at rest were higher in patients compared with controls, but no difference was found in the exercise values. The plasma levels of cAMP correlated closely with plasma catecholamine levels at rest, but not during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Small airways play a key role in the distribution of ventilation and in the matching of ventilation to perfusion. The purpose of this study was to introduce an imaging method that allows measurement of regional lung ventilation and evaluation of the function of airways with a small diameter. The experiments were performed at the Medical Beamline of the European Synchrotron Radiation Facility. Monochromatic synchrotron radiation beams were used to obtain quantitative respiration-gated images of lungs and airways in two anaesthetized and mechanically ventilated rabbits using inhaled stable xenon (Xe) gas as a contrast agent. Two simultaneous images were acquired at two different energies, above and below the K-edge of Xe. Logarithmic subtraction of the two images yields absolute Xe concentrations. This technique is known as K-edge subtraction (KES) radiography. Two-dimensional planar and CT images were obtained showing spatial distribution of Xe concentrations within the airspaces, as well as the dynamics of filling with Xe. Bronchi down to 1 mm in diameter were visible both in the subtraction radiographs and in tomographic images. Absolute concentrations of Xe gas were calculated within the tube carrying the inhaled gas mixture, small and large bronchi, and lung tissue. Local time constants of ventilation with Xe were obtained by following the evolution of gas concentration in sequential computed tomography images. The results of this first animal study indicate that KES imaging of lungs with Xe gas as a contrast agent has great potential in studies of the distribution of ventilation within the lungs and of airway function, including airways with a small diameter.