A noninvasive electromyographic study on threshold and intensity of cough in humans.

The assessment of cough threshold and intensity is important in respiratory medicine. We have developed a method for objectively and noninvasively assessing cough threshold and intensity of expiratory muscle efforts in response to inhalation of ultrasonically nebulized distilled water (UNDW). Thirty (83%) out of 36 volunteers studied coughed in response to UNDW inhalation. Cough threshold was taken as the lowest nebulizer output (mL x min(-1)) that induced cough in two challenges performed at a 30 min interval. At threshold level, repeatability of peak and slope of the integrated electromyographic (IEMG) activity of abdominal muscles was evaluated. Short- and long-term repeatability of cough threshold were evaluated in 15 subjects following a 3 h and a 6-9 month interval, respectively. Dose-response relationships between nebulizer outputs and IEMG-related variables were also investigated, as were the correlations between the latter and expiratory flow during voluntary coughing. The median (1st and 3rd quartile) cough threshold value was 0.89 (0.40 and 1.54) mL x min(-1). At threshold level, peak and slope of IEMG activity were highly reproducible. Cough threshold displayed a high degree of short- and long-term repeatability. Peak and slope of IEMG activity displayed a clear trend to increase (p<0.01) following inhalation of progressively higher UNDW outputs. Maximum flow during voluntary coughs of varying intensity correlated with the peak (p<0.05) and, more closely, with the slope (p<0.01) of abdominal IEMG activity. The assessment of cough threshold as well as the evaluation of the intensity of cough efforts by abdominal integrated electromyographic recordings may represent useful and reliable tools for cough research in humans.

[Physical exercise in the thromboembolism of the pulmonary artery]. / L'esercizio fisico nella tromboembolia dell'arteria polmonare.

In order to evaluate post-embolic pulmonary gas exchange responses to exercise, we studied 7 patients who had previously suffered from an acute pulmonary embolism but were presently free from clinical and functional signs of cardiorespiratory diseases. Patients came to the laboratory on two occasions, 30 and 120 days following the episode of acute embolism, respectively, and performed an incremental ramp exercise test up to the maximum attainable workload. On both occasions, the dead volume/tidal volume (VD/VT) ratio at rest increased. During the first exercise test performed 30 days after the acute pulmonary embolism, mean VD/VT decreased from a resting value of 62.5% to 38.6% at the maximum workload. During the second exercise test, VD/VT decreased, at the same workload, from 71.3% to 35.5%. There was no significant difference in exercise-related VD/VT decrease between the two exercise tests. The results suggest that in patients who have suffered from an acute pulmonary embolism, a considerable pulmonary blood flow redistribution may occur during incremental ramp exercise performed 30 and 120 days after the acute event.

[Medico-legal aspects of chronic respiratory insufficiency under long-term oxygen inhalation therapy]. / Aspetti medico-legali dell'insufficienza respiratoria cronica con ossigeno terapia a lungo termine.

Ninety-one subjects affected by severe pulmonary insufficiency necessitating continuous treatment with oxygen were studied. The social and professional realities and their status within the national health service were determined. The results of the research, obtained through the use of the questionnaires, showed that the lives of these subjects are very much influenced by their pathology. Among the factors considered were necessity for home assistance, scarce or absence of autonomy and contact with the outside world and extremely reduced work capacity. Elevated public spending for assistance was analyzed in reference to public health insurance as regards each single subject and the type of lung dysfunction from which the subject suffered.

Prostaglandin synthesis blockade by ketoprofen attenuates respiratory and cardiovascular responses to static handgrip.

We investigated the effects of prostaglandin synthesis blockade on the changes in breathing pattern, mean blood pressure (MBP), and heart rate (HR) elicited by 3 min of static handgrip at 30% of the maximum voluntary contraction in 12 healthy volunteers. Before each handgrip trial, subjects were treated with intravenous administration of either saline placebo (control) or 1 mg/kg of ketoprofen. Muscle tension and integrated electromyographic activity of exercising muscles remained fairly constant during each trial. In agreement with our earlier findings, during control handgrip minute ventilation progressively increased (P < 0.01) due to a rise in tidal volume and, to a lesser extent, in respiratory frequency. Mean inspiratory flow, MBP, and HR also increased (P < 0.01). End-tidal PCO2 decreased (P < 0.05) during the late phases of control handgrip bouts. Ketoprofen administration reduced serum thromboxane B2 levels (from 57.5 +/- 7.0 to 1.6 +/- 0.4 pg/ml; P < 0.01) and significantly attenuated mean increases in minute ventilation (40.25 +/- 0.60%), tidal volume (37.78 +/- 7.48%), respiratory frequency (55.94 +/- 17.92%), inspiratory flow (42.66 +/- 5.11%), MBP (22.33 +/- 6.82%), and HR (11.04 +/- 2.75%) during the 3rd min of handgrip. End-tidal PCO2 remained close to normocapnic levels. In agreement with previous animal investigations, the present results show that arachidonic acid metabolites are involved in the regulation of the cardiovascular responses to static efforts in humans, possibly through a stimulatory action on muscle receptors. Furthermore, they provide the first experimental evidence that products of the cyclooxygenase metabolic pathway play a role in the mediation of the respiratory adjustments elicited by this form of exercise.

Comparison of dose-response slopes obtained by simultaneous assessment of changes in FEV1 and transcutaneous oxygen partial pressure during methacholine challenges in asthmatic patients.

We aimed to ascertain whether monitoring changes in transcutaneous (tc) oxygen partial pressure (PO2) may be used to determine the slope of the dose-response curves to inhaled methacholine. In 10 adult asthmatic patients, FEV1 and tcPO2 were simultaneously measured during inhalation of doubling methacholine concentrations. In each patient, the slopes of the methacholine dose-response curves for FEV1 and tcPO2 were similar and strongly correlated (r = 0.72; p < 0.05). The results indicate that tcPO2 monitoring represents a useful, reliable tool for analysis of the slope of dose-response curves to inhaled methacholine in asthmatic patients. It can also be used to investigate the pathophysiological implications of bronchial hyperreactivity.

Respiratory and cardiovascular responses to static handgrip exercise in humans.

We studied the time course of respiratory and cardiovascular responses by evaluating changes in the breathing pattern, mean blood pressure (MBP), and heart rate elicited by 3 min of static handgrip at 15, 25, and 30% of the maximum voluntary contraction (MVC) in 15 healthy volunteers. Muscle tension and integrated electromyographic activity remained fairly constant during each trial. During 15% MVC bouts, initially only mean inspiratory flow increased; then, tidal volume and minute ventilation (VI) also rose progressively. No significant changes in MBP and heart rate were observed. During 25 and 30% MVC bouts, not only did mean inspiratory flow, VT, and VI increase but MBP and heart rate increased as well. A slight and delayed rise in respiratory rate was also observed. Unlike 15 and 25% MVC handgrip, 30% MVC handgrip caused a small decrease in end-tidal PCO2. Changes in the pattern of breathing occurred more promptly than those in cardiovascular variables in the majority of subjects. Furthermore, we found a positive correlation between changes in VI and those in cardiovascular variables at the end of 25 and 30% MVC trials. This study indicates that respiratory and cardiovascular responses to static handgrip exercise are controlled independently.

Changes in transcutaneous oxygen partial pressure as an index of response to inhaled methacholine in asthmatic patients.

Bronchoconstriction and hypoxemia have been reported to occur during airway challenges, but the correlation between changes in forced expiratory volume in 1 s (FEV1) and transcutaneous oxygen partial pressure (tcPO2) during methacholine provocation tests has not yet been established (to our knowledge). In 15 symptom-free atopic asthmatic patients and 5 normal subjects, variations in tcPO2 and FEV1 were simultaneously measured during inhalation of doubling methacholine concentrations; the drug concentrations causing a 20 percent decrease in control FEV1 and tcPO2 (PC20FEV1 and PC20tcPO2, respectively) were subsequently calculated. In patients, geometric mean PC20FEV1 and PC20TcPO2 were 1.31 (range, 0.16 to 5.19) and 1.26 (range, 0.29 to 5.82) mg/ml, respectively. In addition, in six patients, methacholine-induced fall in tcPO2 was accompanied by similar changes in arterial PO2. Methacholine inhalation caused no change in tcPO2 or FEV1 in normal subjects. The independent effects of deep breath tests and bronchoconstriction on PC20tcPO2 were studied in five patients challenged on two separate occasions, with and without FEV1 assessment; in these patients, PC20tcPO2 were similar on both the study days. The results indicate that, in asthmatic patients, methacholine-induced bronchoconstriction causes parallel decreases in FEV1 and tcPO2. The tcPO2 monitoring may serve as a tool in the assessment of airway hyperreactivity when active patient's cooperation is scarce.

Anaerobic threshold: reproducibility out from ventilatory parameter estimation.

Anaerobic threshold (AT) during exercise is usually noninvasively determined by assuming a two-segment mathematical relationship between two ventilatory parameters. In the literature, all the possible pairs of segments are first considered, and the most appropriate pair is then selected according to at least-squares method. In such a model, the AT is considered to be related to the joining point of the two segments. In order to test the reliability of the model, we compare the results of the least-squares method to those based on maximum probability method in discriminating the two regression coefficients. In order to test the reproducibility of the two different criteria, comparisons have been repeated after data have been filtered. A paired t test was used to carry out comparisons. Ventilatory parameters were collected in 10 healthy subjects during the use of a bicycle ergometer. The required power was increased every 15 s by steps of 30 W, starting from 50 W. Ve, VO2 and VCO2 have been sampled every 15 s, then the three functions--Ve versus VO2, Ve versus VCO2 and VCO2 versus VO2--were considered. Each function was stylized with two linear segments. Each segment was estimated by using a second-kind linear fitting. We verified that: (i) the AT may be reliably appreciated depending on the pair of selected parameters; (ii) only when data are smoothed is no difference between the two criteria documented (Ve vs. VO2, p = 0.99; Ve vs. VCO2, p = 0.54); (iii) no significant difference, related to smoothing, is documented both in using the least-squares method (Ve vs. VO2, p = 0.61; Ve vs. VCO2, p = 0.15) and the maximum p level criterion (Ve vs. VO2, p = 0.59; Ve vs. VCO2, p = 0.19).

Effect of aminophylline aerosol on the bronchial response to ultrasonic mist of distilled water in asthmatic patients.

To ascertain whether inhaled aminophylline was effective in preventing the bronchial response induced by inhalating of an ultrasonic mist of distilled water (UMDW), we examined 8 asthmatic patients who had previously been shown to be reactive to this agent. Patients were given either 30 mg aminophylline or saline placebo aerosols followed by inhalation of 60 liters of UMDW; measurements of specific airway conductance (sGaw) were made before and after aminophylline or saline administration and after UMDW challenge. UMDW consistently induced a significant decrease in sGaw in all patients; however, in our subjects as a group, the degree of UMDW-induced bronchoconstriction was significantly less after premedication with aminophylline aerosol than after saline (p less than 0.01). Our results suggest that aminophylline is effective in preventing UMDW-induced bronchoconstriction; the possible relationships between bronchial response to UMDW and its modulation by inhaled aminophylline are discussed.

Serum theophylline concentrations and pulmonary function tests after administration of two sustained-release formulations containing theophylline in patients affected by chronic obstructive lung disease.

We compared serum theophylline concentrations in patients treated with one of two commercially available theophylline preparations: a sustained-release aminophylline and a sustained-release theophylline. Two comparable groups of 15 out-patients with stable, chronic obstructive lung diseases were studied: one group was given sustained-release aminophylline while the other took sustained-release theophylline. Both drugs were administered orally for 7 days at a daily dose, equivalent to 12 mg/kg in terms of anhydrous theophylline. Serum theophylline concentrations were always significantly lower after treatment with sustained-release aminophylline than after treatment with sustained-release theophylline, which latter frequently caused undesirable side-effects. Moreover, patients receiving sustained-release aminophylline always showed serum theophylline concentrations lower than 10 mcg/ml. Pulmonary function tests were unaffected by the administration of either drug. We conclude that sustained-release theophylline is more effective than sustained-release aminophylline in terms of induced serum theophylline concentrations. However neither drug was suitable for the treatment of patients with chronic obstructive lung disease without other concomitant therapy.

Bronchoprovocation tests in bronchial asthma and other respiratory disorders: a short review and some personal contributions.

The purpose of this paper, after a brief review of the main features of bronchoprovocation challenges, was to determine whether the administration of an ultrasonic mist of distilled water can influence the bronchial tone of normal subjects and patients affected by various respiratory disorders, in order to assess the effectiveness of this bronchoprovocation test in discriminating between patients. Of the 129 subjects tested 13 were classified as normal, 60 as extrinsic asthmatics, 21 as intrinsic asthmatics, 25 as allergic rhinitics and 37 as chronic bronchitics. Ultrasonic mist, was administered for 5 min and the bronchial response was evaluated in terms of difference between that after the mist minus baseline values of specific airways conductance. The data suggest that the bronchial challenge with ultrasonic mist, a safe, non-pharmacological and simple test, allows a good discrimination between asthma patients and those affected by other respiratory disorders.

Histamine-induced bronchial response after administration of placebo, salbutamol and a combination of a beta-2-adrenergic drug (fenoterol) with an anticholinergic agent (ipratropium bromide) in asymptomatic asthma patients.

We examined 12 non-smoking patients affected by extrinsic bronchial asthma in steady state. Histamine PD20 FEV1 was assessed 4 h after the administration of salbutamol 200 micrograms, a combination of fenoterol 200 micrograms and ipratropium bromide 80 micrograms, and placebo. Despite the absence of any relevant bronchodilator effect, both salbutamol and the combination fenoterol + ipratropium bromide showed a strong protective effect against the bronchial response to histamine compared to placebo, the combination being more effective than salbutamol (p less than 0.05). Our data suggest that, when bronchial challenges with histamine are performed, airway response may be a consequence of both a direct action of such an agent on H1 receptors and of an associated cholinergic reflex.

Comments on subacute and long-term studies.

Long-term therapy with Duovent was always superior in comparison to the other drugs. An immediate efficacy with increasing levels until the 90th day was always obtained. There were no signs of tachyphylaxis and side effects were insignificant. Functional modifications were evident in the large and small airways.

Effects of theophylline-ethylendiamine on chronic pulmonary arterial hypertension secondary to chronic obstructive pulmonary disease.

The use of theophylline in the treatment of chronic lung disease is wide spread thanks to the positive effects on the bronchial tree, on ventilation and on diaphragmatic contractile activity, which are well documented. On the other hand, the cardiovascular effects of this drug have not been studied much, particularly the effects on the hemodynamics of the pulmonary circulation. The latest studies were carried out by Parker (1966 and 1967) and by Jezek (1970) with heart catheterization and by Matthay (1978) with isotopic angiocardiography, but the problem has not been fully explored from the standpoint of pulmonary arterial hypertension. Therefore we are studying the effects of intravenous infusions of aminophylline in patients with chronic obstructive lung disease, trying to examine the effects of this drug on three different groups of patients: the 1st without pulmonary arterial hypertension; the 2nd with latent pulmonary arterial hypertension; the 3rd with evident pulmonary arterial hypertension. We consider pulmonary arterial hypertension as pulmonary arterial pressure greater than 20 mmHg at rest and pulmonary arterial pressure greater than 35 mmHg at the end of 8 min of exercise in the supine position, with 40 W load cycle ergometer. The experimental protocol includes the clinical and functional identification of subjects with chronic obstructive long disease, the performance of right heart catheterization and the cannulation of a peripheral artery, measuring all pressure levels, cardiac output, hemogasanalytic data and theophylline levels in steady state (20-30 min. after the end of invasive manoeuvres) at the 10th, 20th and 30th min after the end of an infusion of 10 mg/kg of aminophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Classification of respiratory functional impairment in chronic obstructive pulmonary disease.

Starting from a paper published in 1964 by Wilson et al., we explored the possibility of classifying the clinical and functional deficit of patients with chronic obstructive lung disease into six classes, class 0 representing normality and class 5 greatest severity. Each symptom or sign was classified into six degrees of increasing severity. Next, we looked for a possible dependence of the collegially assigned score on anthropometric, clinical, or instrumental data in each case. More particularly, we tried (1) to identify such combinations of variables as would permit classification of the patient with the smallest possible error, and (2) to determine which of the variables reflected the severity of the case more faithfully. The results emerging from this study suggest the possibility of evaluating and classifying respiratory impairment in three different ways, as follows: (1) On the basis of clinical data only. This method is the easiest to use and affords a fairly good determination coefficient (R2 = 0.812). (2) Using only some combinations of laboratory data (static and dynamic pulmonary volumes, blood gases, etc.), with or without the addition of vital statistics and anthropometric data. These subensembles would allow a posteriori estimates in cases where the subject is no longer available for questioning and examination. In that case the best multiple regression affords a determination coefficient R2 = 0.82. (3) Using all clinical and laboratory data available. In that case, the best multiple regression (R2 = 0.899) for predictive purposes is that which includes the sum of clinical data, the pulmonary volumes before and after pharmacological bronchodilation, and the PaCO2 value. For practical purposes, however, the most convenient function is the one that includes the sum of clinical data plus FEV1 and RV (R2 = 0.863). Even with the best of the three functions proposed in this paper, however, the standard error of estimate entails tolerance limits sometimes amounting to one whole class of severity. Still, the probability of making an error exceeding one class of severity occurs in only 3.7% of the cases, an average which seems quite acceptable from the clinical point of view.

[The ventilation-perfusion ratio, with special reference to muscular exercise]. / Il rapporto ventilazione/perfusione, con particolare riguardo al lavoro muscolare

The values of VA/Q obtained at rest in 12 normal subjects undergoing cardiac catheterization in a supine position were between 0.63 and 1.695, with a mean of 1.142 +/- 0.295. The VA/Q values obtained in another 10 healthy subjects tested in a sitting position with a rebreathing method for calculating Q. were somewhat less scattered (between 0.77 and 1.50), and also lower (mean 0.975 +/- 0.210). A highly significant correlation was demonstrated during muscular exercise on the bicycle ergometer (sitting position), both between oxygen consumption and alveolar ventilation and between oxygen consumption and cardiac output. However, since at various submaximal work loads cardiac output increased much less than alveolar ventilation, the overall VA/Q ratio showed a progressive increment with increasing oxygen consumption.