Correlation between terbutaline serum levels, c-AMP plasma levels and FEV1 in normals and asthmatics after subcutaneous administration

Terbutaline serum levels, c-AMP plasma levels and percentage improvement in FEV1, were strongly correlated after subcutaneous administration of terbutaline to normals (n = 6) and to asthmatics (n = 5). Changes in c-AMP plasma levels were similar in both normals and asthmatics after subcutaneous administration, denying a systemically beta-adrenergic defect to be present in asthmatics.     

Almitrine has no effect on gas exchange after bilateral carotid body resection in severe chronic airflow obstruction

Using a double-blind cross-over design, a single dose of 100 mg almitrine bismesylate and placebo were administered orally to eight patients with chronic airflow obstruction having undergone bilateral carotid body resection (BCBR) up to two years earlier to alleviate their extreme dyspnoea. In an open study, two other patients have been given almitrine before and three weeks after BCBR. In all patients, arterial blood gases, ventilation and breathing patterns, neuromuscular drive and hypoxic responsiveness have been studied before and three hours after drug administration. Almitrine failed to improve gas exchange in the patients with BCBR, nor did it affect ventilation, ventilatory or hypoxic drive. In the patients studied before and after BCBR, almitrine only improved gas exchange significantly before BCBR. It is concluded that in man almitrine acts solely as a peripheral chemoreceptor agonist and that the well-documented improvement in V/Q relationship is mediated through carotid body stimulation.     

Persistent peripheral airway obstruction in children with severe asthma

We reviewed pulmonary function data on 447 children with the diagnosis of asthma, who were studied in our laboratory over a 6-year interval. We found 19 with evidence of consistent airway obstruction. Two patients who had obvious causes for persistent obstruction were excluded. Seven of the remaining 17 patients consented to further studies. In six of the seven patients studied, flow rates at low lung volumes were severely depressed and remained unchanged after 2 weeks of vigorous "inpatient" therapy. No clinical benefit was apparent. One patient had relentlessly worse disease and died of his asthma. The autopsy revealed changes characteristic of asthma. We conclude that some children with severe asthma have persistent and severe peripheral airway obstruction. These findings challenge the current paradigm that asthma in children is a completely "reversible" illness. Long-term follow-up of children with persistent chronic obstruction may clarify the question of childhood origin of adult lung disease.     

Respiratory airflow pattern in patients with chronic airway obstruction

Previous experimental evidence has shown that in healthy humans inspiratory airflow waveform can be optimized according to minimum rate of work criteria when the respiratory energetic requirements become a substantial fraction of the general metabolism (i.e., during exercise hyperpnea and maximum voluntary ventilation). In patients with chronic airway obstruction (CAO) the relative energetic expenditure devoted to respiration is also greatly enhanced at rest. To investigate the performance of a system also controlling airflow wave pattern in this condition we evaluated by Fourier analysis the harmonic content of respiratory flow waves recorded at rest and during exercise hyperpnea (25 and 50 W on cycloergometer) in 15 patients. The results were compared with those we previously obtained in normal subjects and with some theoretical models. It was found that, while normal subjects display at rest an inspiratory flow waveform reasonably close to a sinusoidal model and adopt a more rectangular and economical flow shape during exercise hyperpnea, patients with CAO show a rather rectangular inspiratory flow shape also at rest, without any remarkable change at higher levels of ventilation. So, in general terms, the airflow pattern employed by patients at rest entails a reduction in the rate of dynamic inspiratory work of about 12% over that required by a sinusoidal waveform, and no further advantage is observed during exercise hyperpnea. Some features of the expiratory flow wave were also analysed. As no model of the respiratory system mechanics presently developed can explain the findings obtained in CAO patients purely on the basis of their altered mechanical parameters, it has been suggested that more complex control of respiratory airflow is operating in this class of patient.     

Early administration of terbutaline in severe pediatric asthma may reduce incidence of acute respiratory failure

BackgroundSevere pediatric asthma, if not immediately and aggressively treated, may progress to acute respiratory failure requiring mechanical ventilation in the pediatric intensive care unit (PICU). Intravenous (IV) terbutaline, a β₂ agonist, is dispensed when the initial treatment does not improve the clinical condition.ObjectiveTo investigate the influence of early initiation of IV terbutaline on the incidence of acute respiratory failure requiring mechanical ventilation in severe pediatric asthma.MethodsA retrospective chart review was conducted of 120 subjects (35 patients from an outside hospital emergency department [ED] with late start of terbutaline and 85 patients from the authors' hospital ED with early initiation of IV terbutaline) admitted to the PICU with severe asthma treated with continuous IV terbutaline. Responses to terbutaline treatment and outcomes were evaluated.ResultsPatients transported from outlying hospital EDs had shorter pre-PICU mean durations of IV terbutaline than those transferred from the authors' ED (0.69 ± 1.38 and 2.91 ± 2.47 hours, respectively, P = .001). Twenty-one of 35 patients (60%) from outlying EDs required mechanical ventilation compared with 14 of 85 patients (16%) from the authors' ED (P = .001). Durations of pre-PICU terbutaline infusion for patients requiring mechanical ventilation were significantly shorter than those with no such requirement (P = .015).ConclusionThe results of the present study, conducted in the largest number of subjects to date, suggest that early administration of continuous terbutaline in the ED may decrease acute respiratory failure and the need for mechanical respiratory (invasive and noninvasive) support in severe pediatric asthma.     

Changes of blood lactate levels after repetitive transcranial magnetic stimulation

The objective was to study whether repetitive transcranial magnetic stimulation (rTMS) of the motor cortex could induce modification of peripheral blood lactate values. Nineteen young healthy volunteers were included; during the study, all subjects were at rest, sitting on a comfortable armchair. The muscular activation was evaluated by continuous electromyographic record. TMS was performed by using a circular coil at the vertex. Resting motor threshold (rMT) was defined as the lowest TMS intensity able to induce motor responses of an amplitude >50 μV in the relaxed contralateral target muscle in approximately 50% of 20 consecutive stimuli. Venous blood lactate values were measured before, immediately after and 10 min after a single session of low frequencies (1 Hz for 15 min) rTMS (LF rTMS) or high frequency (20 Hz for 15 min) rTMS (HF rTMS). As expected, LF rTMS induced a decrease of motor cortex excitability, whereas HF rTMS evoked an increase of motor cortex excitability. However, in the present investigation we observed that both conditions are associated to a significant increase of blood lactate. Since in our experimental conditions we can exclude a muscular production of lactate, the significant increment of peripheral blood lactate values, observed 10 min after the end of the rTMS session, is probably due to the crossing by brain-produced lactate of the blood–brain barrier.     

Changes of histaminopexy in patients with bronchial asthma and chronic urticaria after histaglobin administration

In patients suffering from bronchial asthma and chronic urticaria, the value of histaminopexy was determined prior and after histaglobin treatment (3 injections-1 amp. at 7 days intervals). The value of histaminopexy after histaglobin treatment rised over -240% and was well correlated with the clinical effect of the therapy. These observations are considered as an "ex iuvantibus" evidence that histaminopexy may play a role in the etiopathogenesis of allergic disorders.     

Pulmonary vasodilatation and augmentation of right ventricular function following terbutaline infusion in severe chronic pulmonary disease

Twenty patients with a median age of 61 years and a median forced expired volume in 1 s (FEV1) after bronchodilating therapy of 0.55 l were studied in order to measure the effect of intravenous terbutaline on bronchial tone, cardiac function, pulmonary haemodynamics, gas exchange, and oxygen transport capacity during rest and in 10 patients during exercise. Terbutaline infusion during rest resulted in an increase in heart rate from 84 to 103 beats min-1 (P less than 0.01), a decrease in mean systemic arterial pressure from 95 to 80 mmHg (P less than 0.02), an unchanged mean pulmonary arterial pressure (18 mmHg), an increase in cardiac index from 2.89 to 3.86 l min-1 m-2 (P less than 0.01), an increase in right ventricular ejection fraction from 45 to 53% (P less than 0.01), an increase in left ventricular ejection fraction from 63 to 67% (NS), an unchanged arterial oxygen tension, and an increase in calculated oxygen delivery from 533 to 638 ml O2 min-1 m-2 (P less than 0.01). During exercise terbutaline infusion resulted in an increase in heart rate from 108 to 120 beats min-1 (P less than 0.05), a decrease in mean systemic arterial pressure from 117 to 106 mmHg (P less than 0.01), a decrease in mean pulmonary arterial pressure from 29 to 22 mmHg (P less than 0.01), an increase in cardiac index from 4.53 to 4.64 min-1 m-2 (NS), an unchanged arterial oxygen tension, and an increase in the calculated oxygen delivery from 834 to 856 ml O2 min-1 m-2 (NS). It was concluded that terbutaline augments right ventricular function: increases right ventricular ejection fraction and decreases right ventricular end-diastolic volume, and further decreases pulmonary vascular resistance without decreasing arterial oxygen tension, and increases oxygen delivery in patients with chronic pulmonary disease during rest and exercise.     

Reversibility of airway obstruction in asthma and chronic bronchitis (author transl)

Our purpose was to determine whether, in patients with airway obstruction, the change in the forced expiratory volume in one second (FEV1) which occurs after a bronchodilator drug, is helpful in differentiating asthma from chronic bronchitis. Two groups of patients (48 with asthma and 42 with chronic bronchitis) having a comparable level of initial airway obstruction were selected according to clinical criteria. After salbutamol (200 microgram inhaled) the number of subjects showing a change in FEV1 of at least 20 percent of its initial value or 10 percent of its predicted value was significantly greater (p less than 0.01) in the asthmatic than in the bronchitic group. Lesser changes in FEV1 did not significantly separate the two groups. When the changes in FEV1 were expressed as percentages of both initial and predicted values, the number of positive responses increased in the asthmatic group. However, there were still 20 asthmatics with little or no change in FEV1 after salbutamol who could not be distinguished from the patients with chronic bronchitis. From these data we conclude that, in patients with airway obstruction, a large bronchodilator-induced change in FEV1 strongly suggests the diagnosis of asthma but that the presence of "irreversible" airway obstruction does not disprove it.     

Within-breath respiratory impedance and airway obstruction in patients with chronic obstructive pulmonary disease

OBJECTIVE:Recent work has suggested that within-breath respiratory impedance measurements performed using the forced oscillation technique may help to noninvasively evaluate respiratory mechanics. We investigated the influence of airway obstruction on the within-breath forced oscillation technique in smokers and chronic obstructive pulmonary disease patients and evaluated the contribution of this analysis to the diagnosis of chronic obstructive pulmonary disease.METHODS:Twenty healthy individuals and 20 smokers were assessed. The study also included 74 patients with stable chronic obstructive pulmonary disease. We evaluated the mean respiratory impedance (Zm) as well as values for the inspiration (Zi) and expiration cycles (Ze) at the beginning of inspiration (Zbi) and expiration (Zbe), respectively. The peak-to-peak impedance (Zpp=Zbe-Zbi) and the respiratory cycle dependence (ΔZrs=Ze-Zi) were also analyzed. The diagnostic utility was evaluated by investigating the sensitivity, the specificity and the area under the receiver operating characteristic curve. ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01888705","term_id":"NCT01888705"}}NCT01888705.RESULTS:Airway obstruction increased the within-breath respiratory impedance parameters that were significantly correlated with the spirometric indices of airway obstruction (R=−0.65, p<0.0001). In contrast to the control subjects and the smokers, the chronic obstructive pulmonary disease patients presented significant expiratory-inspiratory differences (p<0.002). The adverse effects of moderate airway obstruction were detected based on the Zpp with an accuracy of 83%. Additionally, abnormal effects in severe and very severe patients were detected based on the Zm, Zi, Ze, Zbe, Zpp and ΔZrs with a high degree of accuracy (>90%).CONCLUSIONS:We conclude the following: (1) chronic obstructive pulmonary disease introduces higher respiratory cycle dependence, (2) this increase is proportional to airway obstruction, and (3) the within-breath forced oscillation technique may provide novel parameters that facilitate the diagnosis of respiratory abnormalities in chronic obstructive pulmonary disease.