Comparability of albuterol delivered by a piezoelectric device versus metered dose inhaler in patients with chronic obstructive airways disease.

In recent years, there has been increased interest in developing propellant-free inhalers for the treatment of patients with chronic obstructive airways disease. Various powder inhalators have been developed. A recent alternative to the dose-metered aerosols has been produced using the piezoelectric effect. This double-blind, double-dummy, randomized, dual-dose, four-period crossover study was designed to compare the effect of albuterol inhaled from the piezoelectric device (PED) and albuterol inhaled from the metered dose inhaler (MDI). The primary efficacy variables were forced expiratory volume in one second (FEV1) and area under the curve (AUC). Although we found a statistically significant device effect for the primary efficacy variables, the two treatments (PED [test] and MDI [reference]) are comparable. The only variable for which comparability was not found was time of onset. We found no dose differences. In conclusion, we found a similar effect of albuterol inhaled by a PED versus an MDI in patients with chronic obstructive airways disease.

Cardiopulmonary function at rest and during exercise after resection for bronchial carcinoma.

BACKGROUND: Measurements of postoperative spirometric values after pneumonectomy and lobectomy vary considerably, and few researchers have studied the changes in exercise capacity during maximal work after lung resection. The purpose of this study was to describe the postoperative alterations in cardiopulmonary function. METHODS: Ninety-seven consecutive patients with lung malignancy were prospectively examined with maximal exercise test, spirometry, and arterial gas tensions. Fifty-seven patients were reinvestigated 6 months postoperatively. RESULTS: In patients having lobectomy, forced expiratory volume in 1 second decreased 8%, and exercise capacity, expressed by maximal oxygen uptake and maximal work rate, significantly decreased 13%. In patients having pneumonectomy forced expiratory volume in 1 second significantly decreased 23%, but the loss in lung volume was partly compensated as measured by exercise capacity, which decreased only 16%. Generally patients with the smallest preoperative forced vital capacity had the smallest postoperative deterioration expressed in percentages. We found a weak correlation between alterations in maximal oxygen uptake and lung function after resection. CONCLUSIONS: Lobectomy is associated with only minor deterioration of lung function and exercise capacity. Pneumonectomy causes a decrease in pulmonary volumes to about 75% of the preoperative values, partly compensated in better oxygen uptake, which postoperatively was about 85% of the preoperative values. Alteration in forced expiratory volume in 1 second is a poor predictor of change in exercise capacity after pulmonary resection.

Exercise testing in the preoperative evaluation of patients with bronchogenic carcinoma.

The aim of this study was to evaluate which parameters of preoperative spirometry and cardiopulmonary exercise test are the best predictors of postoperative morbidity and mortality in patients with bronchogenic carcinoma. Ninety seven patients were prospectively and consecutively examined. All patients had preoperative maximal exercise test and dynamic spirometry. Postoperative complications and causes of death were registered. Logistic regression was used and models explaining the relationship between preoperative variables and postoperative complications and deaths were constructed. We found significant differences in preoperative maximal workload and carbon dioxide output between groups, with and without cardiopulmonary-related complications, but not in spirometry variables. Logistic regression showed maximal workload to be the only predictor of cardiopulmonary complications. Maximal oxygen uptake was predictive of cardiopulmonary deaths. Maximal oxygen uptake and forced expiratory volume were predictive of postoperative complications. A maximal oxygen uptake <50% predicted was associated with high risk of death from cardiopulmonary causes. Kaplan-Meier survival curves showed that maximal oxygen uptake was correlated to long-term survival, while spirometric variables were not. Exercise testing can be used in the preoperative evaluation of patients with nonmetastatic bronchogenic carcinoma. A combination of the results of variables from spirometry and exercise testing is proposed to be used as a preoperative criterion for operability.

Prediction of post-operative cardiopulmonary function using perfusion scintigraphy in patients with bronchogenic carcinoma.

Both ventilation and perfusion scintigraphy are accurate predictors of post-operative ventilatory function. Previous attempts to predict post-operative exercise capacity after lung resection using radioisotope scintigraphy are few and results are conflicting. We studied 32 patients before and 6 months after pulmonary resection for bronchogenic carcinoma to assess the value of lung perfusion scintigraphy for the prediction of post-operative forced lung volumes and parameters on maximum exercise, including maximum ventilation and maximum oxygen uptake. Nine patients were lost to follow-up, and these patients differed from the reinvestigated patients only in the staging of the pulmonary carcinoma and not in preoperative lung function or exercise capacity. We found a clear relationship between the values predicted from a preoperative perfusion scintigraphy, spirometry and a maximum exercise study and the observed values measured 6 months post-operatively. The method underestimated the post-operative values of both spirometric and exercise measurements, especially in the higher range. Only in a few cases were the post-operative observed values less than the predicted values, and in these cases the difference was without clinical significance. Unexpected post-operative respiratory insufficiency was not observed. In conclusion, in patients in whom a pulmonary resection was performed, not only the post-operative spirometric values, but also the more functional related maximum exercise data can be predicted through the knowledge of a preoperative perfusion scintigraphy.

Superoxide anion release from blood monocytes and alveolar macrophages in patients with diffuse lung fibrosis.

Superoxide anion release (O2-) after stimulation with phorbol myristate acetate was measured in alveolar macrophages (AM) obtained by bronchoalveolar lavage and in blood monocytes from 47 patients with diffuse interstitial lung disease: idiopathic pulmonary fibrosis (N = 15), hypersensitivity pneumonitis (N = 7), pneumoconiosis (N = 6) and sarcoidosis (N = 19). Differential cell counts demonstrated a lymphocyte predominance in patients with hypersensitivity pneumonitis (HP) and sarcoidosis while the other groups had neutrophil predominance. No correlation between O2- activity in alveolar macrophages (AM) or blood monocytes (BM) compared to lung function (VC and diffusing capacity) could be demonstrated. Smoking pneumoconiotics had significantly decreased BM O2- release (1.25 +/- 0.25 (SEM) nmol/min/10(6) cells) and significantly increased AM/BM O2- ratios (2.04 +/- 0.26) compared to smokers with idiopathic pulmonary fibrosis (IPF) who had the following mean values: BM O2- release = 2.58 +/- 0.25 and AM/BM O2- ratio = 0.86 +/- 0.23. When matched for sex and smoking, a significantly increased AM/BM O2- ratio was seen among patients with HP (2.19 +/- 0.98) in comparison with patients who had sarcoidosis (0.40 +/- 0.18). Patients with either HP or pneumoconiosis had generally elevated AM O2- release and reduced BM O2- release. These results suggest that environmentally related interstitial lung disorders (HP and pneumoconiosis) may be associated with elevated AM O2- release relative to BM O2- release in comparison to non-environmentally related disorders (IPF or sarcoidosis).

Specificity mapping of patients IgE response towards the tree pollen major allergens Aln g I, Bet v I and Cor a I.

The specificity pattern of IgE from non-treated tree pollen allergic patients (n = 38) were evaluated by solid phase absorption of serum samples followed by CRIE on alder, birch and hazel CIE precipitation profiles. The majority of the serum samples seemed to contain IgE antibodies with the following characteristics: specific towards Bet v I alone and common between Aln g I, Bet v I and/or Cor a I, 'II'. The IgE specificity profiles observed for 95% of the sera tested are compatible with birch pollen allergens being the only sensitizing allergens, indicating that the patients react to allergens from other tree pollens of the Fagales order due to IgE cross-reaction with the major allergens of birch and alder and/or hazel pollens.

[Medium chain acyl-CoA dehydrogenase (MCAD) deficiency: a life-threatening defect of fatty acid oxidation]. / Mellemkaedet acyl-CoA dehydrogenase (MCAD)-mangel: en livstruende fedtsyreoxidationsdefekt.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a potentially fatal metabolic disease, which is characterized by non-ketotic hypoglycemia and lethargy. The disease manifests itself by periodic attacks in connection with infections and periods of fasting, or suddenly as unexpected child death or "near miss". Characterization of a prevalent disease-causing mutation (G985) in the MCAD gene has increased the diagnostic possibilities, since 75% of all patients with MCAD deficiency are homozygous for the mutation. Analysis for this mutation in genomic DNA from a bloodspot on a PKU-card constitute today a certain and specific diagnosis for the disease in 75% of all cases. In the remaining 25% the mutation analysis is supplemented with urine metabolite studies by gas chromatography/mass spectrometry, and with measurements of enzyme activities in cultured skin fibroblasts. The disease is today considered more common than previously anticipated, since the incidence of patients with MCAD enzyme deficiency in Denmark is estimated to 1/27,000 newborns, or two new cases annually. The relationship between the enzyme defect (gene defect) and the clinical expression of the disease is a main subject for the clinical research in the disease at present, because less than 10% of all patients with the gene defect are diagnosed. This applies not only to Denmark but also to other countries.

Bacteria-induced histamine release from human bronchoalveolar cells and blood leukocytes.

Histamine release induced by Staphylococcus aureus was examined in cells obtained by bronchoalveolar lavage (BAL) in non-atopic individuals. Approximately half of the individuals responded with mediator release to the bacterium, and the release was found to be time- and concentration dependent. No difference was found between the patients who responded and those who did not respond in regard to age, sex, smoker/non-smoker, % recovery of BAL-fluid, total cell count, differential cell counts, histamine content per mast cell, or diagnoses. Also stimulation of the BAL-cells with the calcium-ionophore A23187 resulted in histamine release. S. aureus-induced histamine release from basophils was examined in leukocyte suspensions obtained from the same individuals, and in all experiments release was found. The dose-response curves were similar to those obtained with BAL cells. The bacteria-induced mediator release from superficially lying cells in the airways epithelium might be of importance for the precipitation or exacerbation of bronchial asthma in respiratory tract infections.

[Pulse oximetry during fiberoptic bronchoscopy under local anesthesia]. / Pulsoximetri under fiberbronkoskopi i lokalanaestesi.

Pulse oximetry during fiberoptic bronchoscopy in local anaesthesia was performed in 81 patients (52 male, 29 female), median age 60 years (range 25-80); 18 had impaired lung function with FEV1 less than 50%. Premedication consisted of atropine, diazepam and midazolam. The arterial haemoglobin oxygenation (SaO2) was registered continuously. Supplementary oxygen in doses of 2 1/min was administered to 41 patients (group 1), while 40 patients were examined without oxygen (group 2). The two groups were comparable as regards sex, age and lung function. Mean values of SaO2 during bronchoscopy were higher in group 1 (median 96%) than in group 2 (92%) (p less than 0.001). Minimum values of SaO2 were similarly higher in group 1 (median 93%) than in group 2 (87%) (p less than 0.001). The percentage numbers of patients experiencing hypoxaemic episodes with SaO2 less than or equal to 90% and SaO2 less than or equal to 85% were 34% and 5% in group 1 compared to 80% and 35% in group 2, respectively (p less than 0.01). The decrease in SaO2 and the frequency of hypoxaemic episodes were highest in patients with impaired lung function. Supplementary oxygen in doses of 2-3 1/min and pulse oximetry are recommended as routine procedures during fiberoptic bronchoscopy in local anaesthesia.

Immunotherapy with partially purified and standardized tree pollen extracts. I. Clinical results from a three-year double-blind study of patients treated with pollen extracts either of birch or combinations of alder, birch and hazel.

Fifty-four adult patients with tree pollen-induced rhinitis (28), asthma (1), or rhinitis and asthma (25) were selected for immunotherapy with standardized and partly purified tree pollen extracts using a double blind protocol. The selection was based on clinical history, results of nasal or bronchial challenge, skin prick tests and RAST. Further, based on crossed radio-immunoelectrophoresis, sex, age and severity of symptoms, the patients were allocated in matched pairs and the treatment alternatives were randomly distributed within the pairs. Twenty-three patients treated with extracts composed of any combination of alder, birch and hazel pollen which matched their IgE response in CRIE (Group 1 (ABC)) and 22 patients receiving birch pollen extracts (Group 2 (B)) completed all 3 years of treatment. The in vivo results comprising symptom and medicine consumption scores are given here. Changes in specific skin and nasal reactivity as well as in immunological parameters are presented separately. No significant differences were demonstrated between the treatment groups in the two parameters. Both extracts were effective and reduced in general the symptom scores to one tenth of the starting level. Expressed another way, at the end of the study, the patients tolerated 30 times more pollen until symptoms of the same severity were elicited, compared to before. In the Nordic countries, spring-time asthma and rhino-conjunctivitis caused by pollen from deciduous trees can be effectively treated with an extract of birch pollen alone.

Immunotherapy with partially purified and standardized tree pollen extracts. II. Results of skin prick tests and nasal provocation tests from a three-year double-blind study of patients treated with pollen extracts either of birch or combinations of alder, birch and hazel.

Patients allergic to tree pollen entered a 3-year course of immunotherapy (1980-83) with either birch pollen extracts alone (n = 26) or patient-tailored extracts of birch, alder and hazel pollen (n = 27). The clinical and immunological results of this study are published elsewhere. This paper contains an evaluation of skin prick test and nasal provocation test results. There were no significant differences between the two treatment groups concerning these two parameters. In both groups the allergen-specific sensitivity in the skin showed seasonal variations but a significant decrease. During the years of treatment there was also a significant decrease in the specific sensitivity of the nasal mucosa. With the present demands for purification and standardization of allergen extracts it is of practical and economic interest to know that tree pollen-allergic patients showing positive reactions to birch, alder and hazel extracts can be effectively treated using birch pollen extract alone.

Immunotherapy with partially purified and standardized tree pollen extracts. III. Specific IgE response to the major allergens of alder, birch and hazel pollen during immunotherapy.

Patients allergic to pollen from alder, birch and hazel were hyposensitized during a 3-year period with either birch pollen extract alone (n = 24) or a mixture of one or more of alder, birch and hazel pollen extracts (n = 27). The effect of the treatment was evaluated by RAST and tandem crossed-radioimmunoelectrophoresis (tandem-CRIE). The patient' specific IgE response to the major allergens of alder (Aln g I), birch (Bet v I) and hazel (Cor a I and Cor a II), as measured by tandem-CRIE, and the total specific IgE response, measured by RAST, decreased significantly (Pc less than 0.05) during immunotherapy, irrespective of the extract used during the treatment. There was no significant difference (Pc less than 0.05) between the two treatment groups. The results obtained indicate either that birch pollen extract alone is adequate in the treatment of the studied patient group or the patients had been sensitized towards birch pollen alone.

Effect of the nonsedative H1-receptor antagonist astemizole in perennial allergic and nonallergic rhinitis.

We studied the efficacy and side effects of the H1-antihistamine astemizole in perennial rhinitis. We also defined subgroups of responders and examined the added effect of a steroid spray. Fifty-five adults completed a 10- to 14-week controlled trial. Astemizole reduced the number of sneezes to 41% (p less than 0.001) and the number of nose blowings to 55% (p less than 0.001) of the placebo values. The added use of beclomethasone dipropionate caused a further reduction to 14% (p less than 0.001) and 37% (p less than 0.05), respectively. Nasal blockage was only marginally affected by the antihistamine, but it was reduced to 64% by the steroid spray (p less than 0.001). "Sneezers" responded better to the antihistamine than "blockers," with "nose blowers" in an intermediate position. The effect was equal in allergic and nonallergic patients. Astemizole was completely nonsedative but increased appetite and body weight. An open 1-year study of 17 patients demonstrated that astemizole maintained its efficacy and that further weight gain did not occur. It is concluded that astemizole is a highly effective nonsedative H1-antihistamine suitable for continuous therapy of perennial rhinitis.

Fenoterol inhalation powder and aerosol.

The effect of 0.2 mg of fenoterol inhalation powder and 0.2 mg fenoterol from a metered dose inhaler were compared in a double-dummy, cross-over investigation. Ten patients with chronic obstructive lung disease entered the study, which showed no statistically significant difference between the effect of these two forms of the drug on lung function and pulse rate for a period of up to 6 hours after the inhalation of fenoterol. The patients considered the inhalation of powder by means of a commercial inhaler, the Ingelheim inhaler, was simple.

Is is possible to predict the clinical effect of hyposensitization?

Sera from 73 grass pollen allergic patients in two double blind studies on hyposensitization were investigated for IgE response towards one major timothy allergen-antigen 19 (Ag 19) by means of crossed radioimmunoelectrophoresis (CRIE). The clinical efficacy of hyposensitization after initial preseasonal treatment was positively correlated with increase in specific IgE binding to Ag 19. It was possible to predict the clinical efficacy by comparing CRIE performed on sera before and after 3 months of treatment.