Validity and repeatability of the IUATLD (1984) Bronchial Symptoms Questionnaire: an international comparison.

The International Union against Tuberculosis and Lung Disease (IUATLD) Bronchial Symptoms Questionnaire (1984) was developed for use in studies of asthma and its reliability measured in an earlier survey in England. The association of the symptoms elicited by this questionnaire to bronchial response to histamine has also been described. This paper presents the results of studies of the questionnaire in four clinical centres in Europe. The reliability of the questionnaire and its ability to predict the bronchial response to histamine were compared for English, Finnish, French and German translations of the questionnaire in samples of diagnosed asthmatics and controls in Nottingham, Berlin, Helsinki and Paris. The answers to questions showed good repeatability, especially in Finland and Germany, particularly those questions on asthma and wheeze. The most sensitive symptom for predicting hyperresponsiveness was the question on wheeze, the most specific questions were those on waking at night with shortness of breath (Paris and Nottingham) and morning tightness (Helsinki and Berlin). This study shows that the IUATLD (1984) questionnaire may provide useful, valid and comparable data even in translation but these studies will need to be repeated in representative samples before such a possibility is accepted as fully demonstrated.

Behavioral factors in the etiology of asthma.

Evidence for the role of behavior in the etiology of asthma is reviewed here. Behavioral factors have not convincingly been shown to play a part in the inception of asthma. It has been suggested that asthma attacks can be precipitated by conditioning. Previous experiences leading to the expectation that an attack may occur can be regarded as a behavioral factor which may trigger an attack, possibly by inducing hyperventilation. Further research should focus on the possible role of behavioral factors in maintaining a state of hyperreactivity of the bronchi and psycho-immunologic aspects such as brain-controlled neuroendocrine immune mechanisms.

Effect of diltiazem on methacholine-induced bronchoconstriction in extrinsic asthmatics.

The protective effect of the calcium antagonist diltiazem on methacholine-induced bronchoconstriction was investigated in 19 extrinsic asthmatics. A double-blind cross-over design was used (diltiazem vs. placebo, administered orally for 1 week). We found no significant difference between the two treatment regimens when expressed as the provocation dose of methacholine causing a 20% drop in forced expired volume in 1 s (PD20 FEV1). Some individual patients might nevertheless gain some benefit from diltiazem as an additional treatment in difficult-to-manage asthma.

Safety and efficacy of alinidine in symptom-free asthmatics.

Alinidine is a new bradycardic agent which has been shown to be beneficial in the treatment of coronary heart disease. Patients with both coronary heart disease and obstructive lung disease are difficult to treat, because the use of beta-blockers in them is greatly limited by their potential to provoke bronchospasm. Alinidine has no beta-blocking, muscarinic or quinidine-like properties. In a randomized double-blind cross-over study the heart rate reducing effect and safety of alinidine 40 mg p.o. has been examined in 12 symptom-free asthmatics. Alinidine significantly reduced mean heart rate from 81 +/- 10.5 beats/min to 65 +/- 9.7 beats/min two hours after administration. Forced expiratory volume in one second (FEV1), vital capacity (CV), airway resistance (Raw), functional residual capacity (FRC), and specific airway conductance (SGaw) were not affected. It is concluded that alinidine did not influence respiratory function in patients with bronchial hypersensitivity.

Beta-adrenoceptor blockers and terbutaline in patients with chronic obstructive lung disease. Effects and interaction after oral administration.

We studied the effects of a combined treatment with beta 2-stimulating and beta-blocking drugs in 35 patients suffering from chronic obstructive lung disease (COLD) and ischemic heart disease, and/or arterial hypertension. The drugs used were equipotent repeated oral doses of metoprolol (100 mg twice daily [bid]), propranolol (80 mg bid), and a matching placebo for beta-adrenoceptor blockade given in a double-blind and crossover fashion. The intake period of each beta-blocker was two days with consecutive two-day-washout period; 2.5 mg terbutaline and beta-stimulator placebo, respectively, were given throughout the whole trial three times daily (tid). Propranolol alone caused severe deterioration of lung function. After 18 patients had been studied, this drug had to be excluded from the trial. When compared with placebo, metoprolol provoked increasing obstruction, too, but to a significantly lesser degree than propranolol. These negative effects on FEV1 and FRC were completely equalized by terbutaline. Predictive factors for the tolerability of beta-blockers in patients with COLD could not be found. Therefore, careful observations in the initial phase of the treatment with beta-selective blockers are necessary.

[Immunotherapy with BCG and mycobacterial fractions and its use in bronchogenic carcinoma (author's transl)]. / Immuntherapie mit BCG sowie mykobakteriellen Fraktionen und Versuche zur Anwendung beim Bronchialkarzinom.

Animal experiments at the Nat. Cancer Inst. have established that only intra-tumorous application of BCG vaccine has a lasting immunotherapeutic effect on transplantable tumours. However, clinical observations have proved that BCG immunotherapy by the intra-tumorous route increases the incidence of complications, such as allergic reactions and generalized spread of BCG, to an unacceptable level. Ribi has produced a vaccine from mycobacterial fractions which is low in protein and which, as proved in clinical pilot studies in cases of melanoma and cancer of the breast, is so well tolerated that it can be injected into the tumour. Since bronchogenic carcinoma is in the majority of cases inoperable, but, on the other hand, can be reached directly via the bronchoscope or the perthoracic route a pilot study with the Ribi vaccine was started in patients with lung cancer. The preliminary results are reported.

Efficacy of reproterol assessed by the acetylcholine provocation test.

The acute broncholytic efficacy and the protective anticonstrictive effectiveness of a new beta 2-receptor stimulator, Reproterol, was tested in 16 patients with the acetylcholine (ACH) provocation test. Plethysmographic airway resistance determinations (Raw) and flow volume curves (VEmax50%/FVC) were used as assessment parameters. All patients proved susceptible to ACH provocation, in as much they demonstrated a significant rise in the Raw from 2.46 to 11.53 cm H2O/1/sec and a significant decline of the VEmax50%/FVC from 884 to 565 (ml/sec/1) following ACH administration. With Reproterol inhalation (2 puffs at 500 mu each), almost complete elimination of ACH-induced bronchial constriction was achieved. The ACH provocation with the same patients the following day, however, was almost absent 60 min after oral ingestion of 20 mg of Reproterol tablets. Dose-efficacy studies in 7 volunteers from the same group revealed a subjectively better tolerance of the 10-mg tablets, but with a correspondingly lower antibronchia constrictive efficacy.

Dopamine induced hypoxemia in patients with left heart failure.

Previous studies in our laboratory have demonstrated that dopamine produces a significant decrease in arterial PO2 and a mild increase in arterial PCO2 in patients with left heart failure. The present investigations were designed to find out dopamine-induced effects impairing gas exchange. In patients with left heart failure and pulmonary congestion the true pulmonary shunt has been determined by O2-breathing. A statistically significant increase of true shunting could be evaluated. However, from calculations of the components composing AaDO2-air it can be demonstrated that most of dopamine-dependent increase of AaDO2-air is due to an elevated diffusion-distribution gradient. This dopamine effect on arterial PO2 does not limit dopamine application because oxygen administration will outrange the side effect. As changes of ventilation did not occur dopamine is assumed to open up pulmonary vessels producing blood flow in poorly ventilated parts of the lungs and causing an increased disturbance of ventilation/perfusion ratio. The increased true pulmonary shunt can be regarded as result of perfusion of totally unventilated lung areas when dopamine is infused. Haloperidol can attenuate dopamine-dependent decrease in arterial PO2. How haloperidol abolishes this dopamine effect on arterial oxygen tension remains unknown.

[Significance of forced expiratory vital capacity-curves to detect early mechanical alterations in human lungs (author's transl)]. / EinBeitrag zur Bedeutung der forciert ausgeatmeten Vitalkapazität-Kurve für die Früherkennung von Funktionsstörungen in den Atemwegen

In persons who have been smoking cigarettes for many years, who have normal conventional lung function tests the semilogarithmical plotting of forced expiratory vital capacity curves (FEVC) shows statistically significant differences in volume changes below 25 per cent of vital capacity when compared to FEVC-curves of normal subjects of comparable age. On the basis of the equal pressure point theory it is suggested that the simple semilogarithmical plotting of FEVC-curves may reveal early mechanical alterations rather than can be shown by spirometry and airway resistance measurements.

Oxygen affinity of haemoglobin and red cell acid-base status in patients with severe chronic obstructive lung disease.

The oxygen affinity of hemoglobin and the factors determining the position of the oxygen dissociation curve were investigated in twenty-five patients with severe chronic obstructive lung disease. Patients have been separated into three groups: group I showed a normal or mild decrease of PaO2, group II a moderate fall in arterial oxygen pressure, and group III a severe hypoxia with balanced acid-base equilibrium and hypercapnia. Blood hemoglobin exhibited a significant increase in all groups, indicating an improved oxygen transport. In most patients a leftward shifting of the oxygen dissociation curve occurred. It is discussed that the tendency to left shifting is based upon alkalosis inside the red cells, evidently demonstrated in all groups studied. 2,3-diphosphoglycerate showed no close relation to evaluated oxygen affinity of hemoglobin. The evidence for an increased oxygen affinity may reveal a further compensatory mechanism in oxygen transport in patients with pulmonary disorders. Additionally the alkalosis inside the cells may counterbalance too great a right shifting of oxygen dissociation curve in vivo when severe hypoxia and hypercapnia occur.