Bronchial reactivity, lung function, and serum immunoglobulin E in smoking-discordant monozygotic twins.

Smokers with chronic bronchitis and/or chronic obstructive pulmonary disease (COPD) have been reported to have an increased bronchial reactivity (BR). It has been discussed whether increased BR is a risk factor for the development of COPD in smokers. We studied 10 monozygotic twin pairs who were discordant for tobacco smoking by means of histamine provocation tests, lung function tests, and serum samples for total IgE. The smokers had a mild obstructive ventilatory impairment, with FEV1 significantly lower than that of the partner both when it was determined from the flow-volume loops (3.2 +/- 1.0 L for smokers and 3.4 +/- 0.8 L for nonsmokers) and by the Vitalograph spirometer (3.5 +/- 1.0 L for smokers and 3.8 +/- 0.8 L for nonsmokers). Forced midexpiratory flow (FEF25-75%) and forced expiratory flow at 75 to 85% of vital capacity (FEF75-85%) were both significantly lower in the smokers (p < 0.05). The alveolar plateau phase N2-delta test and lung clearing index in the multibreath nitrogen washout test were both significantly affected in the smokers (p < 0.05 and p < 0.01, respectively). We found no significant difference in histamine reactivity between smokers and nonsmokers and no correlation between differences in reactivity and differences in lung function within pairs. Total serum IgE was significantly higher in the smokers than in their nonsmoking siblings. These data suggest that obstructive ventilatory impairment and raised serum IgE are earlier and more constant manifestations of tobacco smoking than increased bronchial reactivity. Thus, bronchial hyperreactivity does not seem to be a major risk factor for the development of early airways obstruction in smokers.

Mucociliary clearance in relation to clinical features in patients with bronchiectasis.

Patients with bronchiectasis were collected from a register covering all hospital stays within the county of Stockholm. They were asked to come for an interview, a clinical examination and to participate in a study of lung mucociliary clearance. The subjects inhaled 6 microns Teflon particles labelled with 99mTc and radioactivity was measured externally. Clearance varied from normal to extremely slow. The average retention of the Teflon particles at 2 h was significantly higher in the 21 patients, 65 +/- 27% (mean +/- SD), than in healthy nonsmokers, 36 +/- 22%. Clearance was more impaired the more generalized the airway symptoms were, the more continuous they were, and the earlier in life they had started; all features which indicate a coherence with the immotile cilia syndrome, an obvious "model disease" in this context. Clearance was studied separately in the two lungs in 18 patients and was similar in both lungs, with one exception.

Mucociliary clearance in relation to clinical features in patients with bronchiectasis.

Patients with bronchiectasis collected from a register covering all hospital stays within the county of Stockholm were asked to participate in a study of lung mucociliary clearance. Twenty-one patients inhaled 6 um Teflon particles labelled with 99mTc and radioactivity was measured externally. The patients were also clinically classified. Clearance varied from normal to extremely slow. The average retention at 2 hours was significantly higher in the patients, 65+27%, (mean +/- SD) than in healthy nonsmokers, 36+22%. Clearance was more impaired the more generalized the airway symptoms were, the more continuous they were, and the earlier in life they had started, all features which indicate a coherence with the immotile cilia syndrome, an obvious "model disease" in this context. Clearance was studied separately in two lungs in 18 patients and was similar in both lungs with one exception. A full presentation of this investigation is submitted to Eur. J. Respir. Dis.

The immotile-cilia syndrome compared to other obstructive lung diseases: a clue to their pathogenesis.

Twentyfour adults, aged 19-47 years, with congenitally nonfunctioning cilia were investigated by clinical examination, radiography, spirometry, and in most cases by tracheobronchial clearance measurements and ultrastructural examination of respiratory tract cilia and/or sperm tails. They all suffered from chronic bronchitis, rhinitis and sinusitis, and most of them had bronchiectasis and a history of otitis. Most had spirometrically overt obstructive lung disease and four radiological signs of emphysema. Clinical profile, lung function and mucociliary clearance data were compared to corresponding data from samples of patients with other obstructive lung diseases. These comparisons indicate that a long-standing impairment of mucociliary clearance is of pathogenetic importance in common chronic obstructive lung disease associated with chronic bronchitis, but not in emphysema associated with severe alpha 1-antitrypsin deficiency without chronic bronchitis, and not in asthma. In cystic fibrosis and in hypogammaglobulinemia an impaired clearance is not of primary pathogenetic significance but may contribute to the development of obstructive lung disease.

Tracheobronchial clearance after flexible fiberoptic bronchoscopy.

As the tracheobronchial mucosa is vulnerable to mechanical trauma it is important to investigate whether examination with a flexible fiberoptic bronchoscope (FFB) damages the respiratory mucosa. In 12 subjects, tracheobronchial clearance was measured 1 day before and 1 day after FFB performed under topical anaesthesia. Mucociliary transport was studied by having the patients inhale 6 micron teflon particles tagged with 99mTc, and by external measurements of the radioactivity retained in the lungs. Most of the patients had a similar clearance on both days. A marked impairment after FFB was only seen in one patient. This study suggests that the tracheobronchial clearance system has a large reserve against mechanical trauma. FFB may possibly change mucociliary clearance in some patients, and this can be of practical significance in patients unable to cough.

On the pathogenesis of obstructive lung disease. A study on the immotile-cilia syndrome.

The role of mucociliary transport in man can be evaluated by studying persons with the recently recognised "immotile-cilia syndrome". Such persons have chronic or recurrent infections of the upper and lower airways and have ultrastructural defects of cilia and sperm tails. Men suffering from the syndrome usually are sterile and have immotile spermatozoa. About half of the subjects have complete situs inversus. Fourteen persons with the immotile-cilia syndrome have been studied here in an attempt to evaluate the role of an impaired mucociliary transport for the development of obstructive lung disease. Age range was 25-40 years; there were ten men and four women. Mucociliary transport in the lungs was extremely slow in all subjects. Spirometry demonstrated airway obstruction in nine subjects. Two of these subjects had radiological evidence of pulmonary emphysema. The results indicate that an absent mucociliary transport predisposes to the development of obstructive lung disease. Patients with classic chronic bronchitis have earlier been shown to have a severely impaired mucociliary transport. The present findings in subjects with primary ciliary immotility make it probable that this impaired mucociliary transport is of pathogenetic importance for development of the obstructive lung disease often found in patients with chronic bronchitis.

Cystic fibrosis compared with the immotile-cilia syndrome. A study of mucociliary clearance, ciliary ultrastructure, clinical picture and ventilatory function.

Patients with cystic fibrosis (CF) were investigated for mucociliary clearance (with and without stimulation by terbutaline), clinical picture, ventilatory function and ultrastructure of cilia. The results were compared with those of patients with congenitally immotile cilia (immotile-cilia syndrome). Mucociliary clearance could be demonstrated in all the seven CF patients who succeeded in inhaling the test aerosol. Ciliary ultrastructure from a deceased CF patient was normal. Patients with the immotile cilia syndrome had no substantial clearance and defective cilia. The CF patients coughed more during the clearance measurements than any other group studied earlier, and their coughing was effective. One patient succeeded in avoiding coughing in both measurements and had faster clearance when he got terbutaline than when he got the vehicle. Although younger, the CF patients tended to be more obstructed in their lungs and more handicapped than the patients suffering from the immotile-cilia syndrome. The latter patients had more discomfort from rhinitis, sinusitis and otitis than had the CF patients. An impairment of the mucociliary transport rate is hence unlikely to be a primary pathogenic factor for the respiratory tract disease in CF patients.

Working capacity and cardiopulmonary function after extensive lung resections.

Twelve patients were investigated 7-168 months after pneumonectomy. Two of them had also undergone resection of a segment of the remaining lung. The follow-up included studies of working capacity, static and dynamic lung volumes, alveolar gas exchange, diffusing capacity, blood gases and central haemodynamics with right heart catheterization. The working capacity was markedly reduced, limited by dyspnoea in 10/12 patients. The dyspnoea was related to reduced static and dynamic lung volumes (50% of normal). The diffusing capacity of the remaining lung was half of that predicted for two lungs from total haemoglobin and age and the transfer capacity of the lungs for oxygen was loaded to its maximum even at submaximal loads, resulting in a decrease in arterial oxygen tension and saturation and an increase in the alveolo-arterial oxygen tension difference. The central circulation was hypokinetic at submaximal loads and the stroke volume was small. The reduction in working capacity was caused by a number of coacting factors, inactivity, reduced lung function and small stroke volume. It was not possible from the present investigation to single out any of these factors as the main cause of dyspnoea during exercise and thereby the reduced working capacity.