Deposition and clearance in large and small airways in chronic bronchitis.

Tracheobronchial clearance was studied twice in 16 patients with chronic obstructive bronchitis after inhalation of 6 microns (aerodynamic diameter) monodisperse Teflon particles labeled with 111In. At one exposure the particles were inhaled at an extremely slow flow, 0.05 L/s; at the other they were inhaled at a normal flow, 0.5 L/s. Theoretical calculations and experimental data in healthy subjects indicate particle deposition mainly in the smallest ciliated airways using 0.05 L/s, i.e., in the bronchiolar region, and an enhanced deposition in larger airways using 0.5 L/s. Lung retention was measured at 0, 24, 48 and 72 h. Clearance was significantly every 24 h for both exposures (p < .05). The fractions of retained particles were significantly larger for particles inhaled at 0.05 L/s compared to 0.5 L/s at all points of time (p < .001). Compared to healthy subjects, the retained fractions of deposited particles were larger in patients with bronchitis breathing at 0.05 L/s, but smaller with breathing at 0.5 L/s (p < .01). Significant relationships were found between lung retentions and airway resistance (Raw) at 0.5 L/s, r = -.68 (p < .01), but not at 0.05 L/s, and between lung retention at 24 h and weight of expectorated sputum at 0.05 L/s, r = -.50 (p < .05). There was, furthermore, an almost significant relationship between sputum volume and rate of tracheobronchial clearance between 0 and 24 h (in percentage of the total amount cleared during 72 h) at 0.05 L/s, r = .42 (p = .05). The results indicate that in patients with chronic bronchitis overall clearance of particles in small airways is incomplete, as compared to larger airways. An increased amount of mucus, however, seemed to improve clearance of peripherally deposited particles, possibly by making cough more effective in small airways.

Repeatability of airway deposition and tracheobronchial clearance rate over three days in chronic bronchitis.

Previous investigations on tracheobronchial clearance in chronic bronchitis or chronic obstructive pulmonary disease (COPD) have usually referred to measurements during a short time-period, i.e. a few hours. The purpose of this study, therefore, was to study regional particle deposition and tracheobronchial clearance during 72 h. In 14 patients with chronic bronchitis clearance of 111In-labelled 3.6 micrograms Teflon particles and lung function were measured on two occasions, with an interval of 2 weeks. Lung retention of test particles was measured at 0, 24, 48 and 72 h using a profile scanner. The weight of expectorated sputum samples was measured after the two clearance measurements. The particle retentions at all time-points were reproducible, as seen from the two measurements ( r > 0.90). The fast clearance phase was completed within 72 h. No correlation between sputum volume and clearance was seen. There was a significant negative correlation between airway resistance and the 72 h retention (r= -0.66), and an even better correlation between specific airway resistance and the 72 h retention (r = -0.82), indicating more central deposition in obstructed airways. There was no significant correlation between lung function tests reflecting smaller airways and the 72 h retentions. Deposition data agreed well with theoretical calculations and experimental data in healthy subjects. In spite of earlier findings that mucociliary transport is usually severely impaired in chronic bronchitis and COPD, the present results indicate that overall tracheobronchial mucus clearance in these patients is fairly effective, probably due to a productive cough. Alveolar deposition may be estimated by measurements of the 72 h retention in subjects with chronic obstructive pulmonary disease. The 72 h retention is dependent mainly on the calibre of larger airways. The present method of studying airway clearance during 3 days is highly reproducible.

Effect of protriptyline, 10 mg daily, on chronic hypoxaemia in chronic obstructive pulmonary disease.

A daily dose of 20 mg of protriptyline can improve daytime arterial blood gas tensions in chronic obstructive pulmonary disease (COPD). Its usefulness is limited by anticholinergic side-effects. This study examined whether a daily dose of 10 mg of protriptyline improved daytime arterial oxygen tension (PaO2) and quality of life in patients with stable mild or moderate hypoxaemia caused by COPD. Twenty six patients were randomized to receive protriptyline or placebo in a double-blind parallel-group trial for 12 weeks, following a run-in period of 4 weeks, in order to assess the stability of hypoxaemia. Patients with a change in PaO2 of > 0.7 kPa during the run-in were excluded. Spirometry, quality of life and dyspnoea score were measured at randomization and after 12 weeks, whilst arterial blood gas tensions were also measured 2 and 6 weeks after randomization. No improvement in arterial blood gas tensions, spirometry values, dyspnoea score, or quality of life was found in either the protriptyline or the placebo group. The majority of patients receiving protriptyline experienced anticholinergic side-effects, which necessitated the withdrawal of the drug in one patient. We conclude that there was no evidence that a daily dose of 10 mg of protriptyline had a significant effect on daytime arterial oxygen tension in stable mild and moderate hypoxaemia caused by COPD. Despite the low dose, anticholinergic side-effects occurred in most patients.

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.

Methylations in hemoglobin from monozygotic twins discordant for cigarette smoking: hereditary and tobacco-related factors.

Dose monitoring of exogenous methylators by measurement of N-methylvaline in hemoglobin (Hb) is rendered difficult due to a relatively high, variable background in unexposed persons. A kinetic study indicates intracellular S-adenosylmethionine to be a main source of these background methylations. A comparison of twin pairs indicates that the variation in methylvaline levels is partly hereditary (P less than 0.001). Therefore, in a study of monozygotic twin pairs discordant for tobacco smoking the resolving power of the monitoring was increased and in vivo doses of methylators from the smoke could be more easily monitored through their adducts to Hb. Probably, twin studies offer a useful tool for the identification and quantification of electrophiles of endogenous and exogenous origin.

Bronchial reactivity and allergy-promoting factors in monozygotic twins discordant for allergic rhinitis.

Bronchial reactivity was studied twice in eight monozygotic twin pairs discordant for allergic rhinitis with pollen hypersensitivity, during the winter season (all eight pairs) and during the pollen season (seven pairs). On both occasions, the allergic twins showed significantly higher reactivity than their nonallergic siblings. The results indicate that moderate allergic rhinitis is associated with increased bronchial reactivity. This increased reactivity is an acquired trait; however, bronchial reactivity is not constantly increased in pollen rhinitis and may be normal even during the pollen season. The symptoms of allergic rhinitis usually started in childhood before the separation of the siblings. We could not demonstrate any major differences in exposure to allergens or airway irritants between the siblings. The allergic twins tended to have lower birth weight and insufficient weight increase just after birth.

Bronchial reactivity and atopy in asthma discordant monozygotic twins.

Bronchial reactivity was studied in six asthma-discordant monozygotic twin pairs. In four pairs, atopy was confirmed in the asthmatic twin. It was not confirmed in any of the nonasthmatics. In five pairs, the asthmatic twin was markedly more reactive than the nonasthmatic partner. Bronchial reactivity correlated significantly with total IgE. The results indicate that hyperreactivity and atopy were acquired.

Tracheobronchial clearance in asthma-discordant monozygotic twins.

Tracheobronchial clearance and bronchial reactivity were studied in 6 asthma-discordant monozygotic twin pairs, and in 3 concordant pairs as controls. Clearance of 6-microns Teflon particles labeled with 99mTc was followed for 2 h. The results indicate that clearance in the larger airways is usually not severely impaired in mild to moderate asthma, and that it may be increased as well as decreased. Bronchial reactivity correlated with clearance in the nonasthmatics.

Influence of ambroxol on tracheobronchial clearance in simple chronic bronchitis.

The influence on tracheobronchial clearance of ambroxol, a metabolite of bromhexine, was investigated by measuring the lung retention of inhaled 6 micron monodisperse Teflon particles labelled with 99mTc. Fourteen subjects with simple chronic bronchitis, who belonged to a "responder" group in an earlier study on the subjective effects of ambroxol, were examined using a double-blind cross-over design comparing 120 mg ambroxol daily and placebo. On commencing the study and after each 2-week treatment period, the subjects were examined for mucociliary clearance and clearance by voluntary coughing. Treatment did not influence mucociliary clearance or clearance by cough. There is still a possibility that phlegm loosening by cough is enhanced in situations with more hypersecretion.

Ambroxol and simple chronic bronchitis. Effects on subjective symptoms and ventilatory function.

In a double-blind, randomized, controlled trial using parallel groups, we evaluated the effects of two dose levels of ambroxol (60 and 120 mg daily) versus placebo by means of pulmonary function tests, patients' diary cards, interviews on current airway symptoms and subjective drug effects in 92 subjects with simple hypersecretory chronic bronchitis. The treatment period was 2 weeks. Subjects in the 120-mg group compared to the placebo group reported improvement in respiratory symptoms (p less than 0.05), particularly in phlegm loosening (p less than 0.05) and tended to prefer the treatment period when compared to placebo (p = 0.056). Lung function values and diary cards did not indicate significant changes.

Ambroxol therapy in simple chronic bronchitis: effects on subjective symptoms and ventilatory function.

Ambroxol, a metabolite of bromhexine, was investigated in a double-blind, controlled trial using parallel groups. We studied the effects of 60 mg and 120 mg daily versus placebo in subjects with simple chronic bronchitis. Possible therapeutic effects were evaluated by means of interviews on subjective drug effects and current respiratory symptomatology, patient diary cards, and lung function tests. Ninety-seven subjects entered the study and 92 completed satisfactorily. Comparison with the placebo group at the end of the study showed that significantly more subjects in the 120 mg ambroxol group reported improvement in respiratory symptoms, principally improved expectoration. Subjects in the 120 mg group tended to prefer the treatment period when compared to placebo but the diary cards did not indicate significant changes. Lung function values were mainly normal and did not change during treatment. We conclude that the drug had a symptomatic effect and that further studies in more severely affected patients would be worthwhile.

Routine use of counterimmunoelectrophoresis for the detection of pneumococcal antigen in sputum.

Sputum samples obtained routinely for culture from patients at a thoracic department were also examined for pneumococcal antigen by means of counterimmunoelectrophoresis (CIE), using a polyvalent antipneumococcal type serum (omniserum). Pneumococci were found in 1.3% of the 880 cultures, whereas pneumococcal antigen was detected with CIE in 6.5%. The validity of these findings was tested by correlating them with the presence of clinical symptoms in those with positive tests and also by antigen detection in ELISA using monoclonal antibodies specific for the C-polysaccharide common to all types of pneumococci. Clinical findings corresponding to confirmed or probable current chest infection were found in 36 of the 48 patients with positive CIE. ELISA was positive in 33 of the 38 patients with positive CIE who were tested. Although the study deals with an unselected material of chest patients, it indicates that CIE is a sensitive method and that it is independent of current antibiotic treatment. Pneumococcal infection is probably of importance in exacerbations of chronic obstructive lung disease, but the clinical usefulness of detecting pneumococcal and other antigens in this patient group needs to be studied further.

A comparison of sustained-release terbutaline with ordinary salbutamol in bronchial asthma.

The effects of a sustained-release preparation of terbutaline, depot tablets, 7.5 mg 2 times/day were compared with ordinary salbutamol tablets 4 mg 3 times/day. The study, performed for 2 weeks, one week on each treatment, was double-blind, double-dummy, crossover with randomized allocation of the drugs. Twenty-five patients with chronic bronchial asthma completed the trial. The morning Peak-Flow was higher during the period on the depot tablets compared to that on the ordinary tablets (p less than 0.05). No differences were found in side effects.