Relationship between the airway response to inhaled sulfur dioxide, isocapnic hyperventilation, and histamine in asthmatic subjects.

To determine whether bronchoconstriction induced by sulfur dioxide can be predicted by the airway response to inhaled histamine, we exposed on two days 46 patients with asthma to air or 0.5 ppm SO2. The exposure protocol consisted of 10 min of tidal breathing followed by 10 min of isocapnic hyperventilation at a rate of 30 l/min. Airway response was measured before (baseline) and after hyperventilation in terms of specific airway resistance, SRaw. Exposure to air increased baseline mean (SD) SRaw from 6.27 (2.12) to mean (SD) maximum post-hyperventilation SRaw of 9.10 (4.38) cmH2O*s (P less than 0.0001). Exposure to SO2 increased mean (SD) baseline SRaw from 6.93 (3.29) to mean (SD) maximum post-hyperventilation SRaw of 18.21 (18.69) cmH2O*s (P less than 0.0001). Mean (SD) effect of SO2 defined as difference between maximum post-hyperventilation SRaw after SO2 versus air was 9.11 (16.14) cm H2O*s. When evaluated individually, 26 and 34 of the 46 patients showed an airway response to hyperventilation of air and SO2, respectively. Airway response to histamine was determined as the histamine concentration necessary to increase specific airway resistance by 100%, PC100SRaw. The airway response after SO2 and PC100SRaw showed a weak but significant correlation (R = -0.48), whereas the responses to hyperventilation and SO2 did not correlate. We suggest that the mechanisms by which histamine and SO2 exert their bronchomotor effects are different and that in asthmatic patients the risk of pollutant-induced asthmatic symptoms can be poorly predicted by histamine responsiveness.

[Maximum immission concentrations and maximum allowable concentrations and their significance in the evaluation of indoor conditions]. / MIK-und MAK-Werte und ihre Bedeutung zur Bewertung von Innenraumsituationen.

In the work-place environment MAK values (maximum allowable workplace concentrations) haven been fixed as time-integrated averages relatively early in order to avoid adverse health effects to workers exposed to air pollution during their working shift. Similarly, MIK values (maximum immission concentrations have been set up to protect the health of the total population. In contrast to this, there are no limit values for pollutant concentrations in non-working place indoor environments. The problem of applying the MIK and MAK value concept to the non-industrial indoor environment is discussed. In this context, mention is also made of the possibility of an indirect uptake of deposited dust or of a diffusion of gaseous components into foodstuff and of other exposure pathways. The discussion shows that the reference to MIK and MAK values can only lead to a first approximation in the evaluation of a non-industrial indoor situation. Further studies are needed to establish limit values for special indoor air pollutants. In this context, the usefulness of the concept of the so-called BAT value for indoor purposes is discussed (BAT = Biologischer Arbeitsstoff-Toleranzwert). It will be an urgent matter to set up emission standards for building materials, furniture, textiles, paints and other possible emitters in order to protect the population from preventable exposure.

Hemodynamic response to graded water immersion.

Hemodynamic response to graded immersion was studied in healthy male subjects in a thermoneutral bath in the sitting position. Pressures in the right heart and cardiac output were determined by means of a semifloating catheter with a thermistor probe. Pressures in the right atrium, pulmonary artery and in pulmonary wedge position increased with increasing depth of immersion, cardiac output was likewise augmented. Heart rate decreased from rest to hip immersion but remained constant from hip to head out water immersion. Plasma norepinephrine concentration remained constant throughout the experiment. The reported changes depend on the blood shift from capacitance vessels into the thoracic cavity. From this, preload increased and cardiac performance was improved. However, in patients with disturbed left ventricular function, immersion to the neck may be potentially hazardous due to augmented left ventricular filling pressure.

Determination of respiratory resistance by an oscillation method. Studies of long-term and short-term variability and dependence upon lung volume and compliance.

The respiratory resistance (Ros) as measured by an oscillation method, and the airway resistance (Raw) as measured by body plethysmography were determined in 10 healthy volunteers thrice daily every week over a period of 22 weeks. Ros in 9 of this group was measured at different breathing levels at constant respiratory rate and volume. Additionally, the phase angle between oscillatory pressure and flow (phi), the thoracic gas volume, the end-tidal volume, the functional residual capacity, Raw and the lung compliance were determined. Furthermore Ros of 116 patients was measured together with the lung and thorax compliance. Compared to Raw, the variability of Ros is smaller and the sensitivity is higher. There is a reciprocal relationship between Ros and lung volume, lung compliance, and compliance of the lung and thorax system. Therefore, measurements of Ros should be performed at a normal, stabilized mean breathing level.

Effects of NO2 on chronic bronchitics.

The acute influence of NO2 on mechanics of breathing and respiratory gas exchange was investigated in a total of 111 subjects, aged 25 to 74 years, with chronic nonspecific lung disease (CNSLD). They breathed NO2-air mixtures containing 0.5 to 8.0 ppm NO2 for up to 15 to 60 min. Additionally in nine subjects the protective action of atropine, meclastine, and orciprenaline was investigated. While the alveolar PO2 remained constant during inhalation of 5 and 4 ppm NO2, a significant decrease of the arterial PO2 and a corresponding increase of the arterial to alveolar PO2 gradients occurred. Inhalation of 2 ppm NO2 had not such an effect. Inhalation of NO2 at concentrations down to 1.5 ppm resulted in a significant increase of airway resistance. Lower concentrations had no significant effect. Prolongation of the exposure period from 15 to 60 min at a NO2 concentration of 5 ppm did not result in a more pronounced disturbance of the respiratory gas exchange for oxygen beyond the extent observed after exposure to 5 ppm NO2 for 15 min. Meclastine, in comparison with orciprenaline and atropine, showed a pronounced protective effect on the negative impact of NO2 on respiratory gas exchange and airway resistance. It is concluded that NO2 may act by release of histamine, causing a bronchiolar, alveolar, and interstitial edema, thus differing from irritant air pollutants like SO2, where reflex bronchoconstriction causes in some bronchitics dramatic increases of airway resistance at similar low concentrations.

Possible mutagenic properties and carcinogenic action of the irritant gaseous pollutants NO2, O3, and SO2.

Carcinogenic or cocarcinogenic effects of NO2, O3, and SO2 have not been proven to date with sufficient reliability. However, nitrosamine formation after exposure to NO2- or O3-induced decrease in benzpyrene hydroxylase are potential hazards. A final revaluation of a possible cocarcinogenic action of SO2 requires further experimental studies.

[Respiratory gas exchange during breathing of O2 in different inert gases (author's transl)]. / Respiratorischer Gasaustausch bei Atmung von 20,9% Sauerstoff in verschiedenen Inertgasen.

In 15 patients with chronic bronchitis with or without emphysema breathing of room air was compared with breathing of 20.9% O2 in helium and in argon. Minute ventilation and alveolar ventilation showed no differences, whereas the alveolar and arterial pO2 and PCO2 showed an improvement of the CO2 gas exchange and a deterioration of the O2 gas exchange. This contradictory behaviour cannot be explained by shunts or inhomogeneities or influence of gaseous or alveolo-capillary diffusion. Perhaps the physicochemical properties of the alveolo-capillary membrane change by the depletion of nitrogen. The recommendation of helium-oxygen breathing, proposed by other authors for patients with obstructive airway diseases, cannot be supported, when the gas exchange for O2 is deteriorated.

Use of isoproterenol infusion to study intrapulmonary gas mixing in man.

In the present investigation, the effect of an increased cardiac output on intrapulmonary gas mixing was studied in healthy male subjects. Increase of heart rate and cardiac minute output was induced by infusion of isoproterenol, intrapulmonary gas mixing was analyzed by simultaneous washout of inert gases widely differing in molecular weight (helium and sulfur hexafluoride). Parameters, appropriate to indicate quality of gas mixing, have been crossover point (COP) and separation index (SI). During isoproterenol-induced tachycardia, the COP occurred earlier and the SI decreased. Both changes then demonstrate an improved gas intrapulmonary mixing. The movement of the heart reduces stratified inhomogeneity.

Heart rate and perceptual response to exercise with different pedalling speed in normal subjects and patients.

The perceived exertion rating (RPE) scale of Borg was used to investigate the relationship between perceived exertion and pedalling rate. Normal subjects and patients with chronic obstructive lung disease (Cold) were studied in repeated test series. Work load, applied in a random order, varied from 2.5 to 10 mkp/s (patients) and 5 to 20 mkp/s (normals). Pedalling rate varied from 2.5 to 10 mkp/s (patients) and 5 to 20 mkp/s (normals). Pedalling rate varied from 40 to 60, 80, 100 rpm. At constant work load, RPE decreases during increasing pedalling rate. With respect to validity, RPE, showing a closer relationship to work load than to heart rate, seems to reflect perception of physical stress rather than perception of physiological strain. In addition, the results raise the question of standardization of pedalling rate in bicycle ergometry.