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Maximal expiratory flow-volume curves and spirometry were measured in 49 white, nonsmoking, asymptomatic men 19 to 23 yr of age and 179 to 184 cm tall. Because of the uniformity of sex, age, height, and ethnic group, conventional predicted values for these men were virtually identical. Nevertheless, the between-subject coefficient of variation in spirometric and maximal flow results varied from 10% for vital capacity (VC) and forced expiratory volume in one second (FEV1) to 29% for maximal flow when 25% of VC remained to be expired. Confirming previous results, between-subject coefficient of variation was not reduced by expressing flow as VC/s instead of L/s. Eighteen of these men had standard posteroanterior and lateral chest radiographs to measure tracheal diameters at total lung capacity. Both tracheal cross-sectional area and anteroposterior diameter were positively related to FEV1 (r = 0.73, p = 0.001), the relationship being slightly stronger than with peak expiratory flow. There was a trend for VC also to be related to tracheal dimensions. As 50% of residual between-subject variation in FEV1 in these men was accounted for by variation in tracheal size, predicted values of FEV1 in an individual subject might be usefully refined by measuring tracheal size in epidemiologic surveys, thus allowing interpretation of small deviations from mean predicted values. Further studies are required on the variation in tracheal size in a more heterogeneous population.

Transit time analysis has been proposed as a simple and sensitive method for detecting slowing and non-uniformity of lung emptying in airway disease. We have measured the first moment (alpha 1, mean transit time) and second moment (alpha 2) about the origin of the forced expiratory spirogram in 202 men (53 non-smokers, 149 regular smokers). Values of alpha 1 and square root alpha 2 (calculated from the first 6 s of expiration) increased with age in both smokers and non-smokers and were significantly greater in older smokers than in non-smokers. The rate of increase in alpha 1 and square root alpha 2 was most rapid in smokers between 24 and 36 years. Changes in alpha 1 were closely related to changes in FEV1/FVC ratio. Values of square root alpha 2 were frequently slightly increased in young smokers and in older smokers without definite abnormality of FEV1/FVC or alpha 1, probably because square root alpha 2 is more strongly influenced by the final part of the spirogram. Problems persist in determining the best method for expressing abnormality in square root alpha 2, in allowing for premature termination of the spirogram and for assessing dispersion of transit times. We conclude that square root alpha 2 demonstrates abnormalities not detected by alpha 1, in many young smokers and in older smokers with no or only slight increase in alpha 1. Once alpha 1 is definitely increased, measuring square root alpha 2 provides little additional information.(ABSTRACT TRUNCATED AT 250 WORDS)

In 10 excised dog lobes we measured total lobar resistance (Rlo) by forced oscillation at various transpulmonary pressures (Ptp) before and after bronchodilators and obtained simultaneous tantalum bronchograms in 5. Mean airway diameter increased up to a Ptp of 30 cmH2O, although the increase was greater between 0 and 10 cmH2O. In contrast, Rlo decreased between 0 and 10 cmH2O but increased again between 10 and 30 cmH2O. At a Ptp of 30 cmH2O, the mean diameter of small airways (< 2 mm) increased 31%, that of large airways (> 7 mm) 2% after aerosolized bronchodilators. At a Ptp of 1 cmH2O, increases were 44 and 15%, respectively. Values of Rlo were reduced at all Ptp after bronchodilator, but minimum Rlo occurred at lower Ptp than before, and the absolute increase in Rlo at greater Ptp was preserved. In four additional lobes, we partitioned Rlo using a retrograde catheter. All of the increase in Rlo at large Ptp was peripheral to the retrograde catheter. We conclude that excised lungs have bronchomotor tone that narrows airways even at high Ptp and that loss of tone magnifies the relative increase in Rlo at high Ptp, supporting suggestions that the increase is due to tissue resistance and hysteresis.

We examined the volume history effect on maximal expiratory flow (Vmax) in patients with asthma by comparing Vmax at 60% of VC from forced exhalation maneuvers begun just above FRC (partial, P) with those begun from TLC (maximal, M) and expressed the results as M-P ratios. In a clinic population with varying degrees of obstruction, we found that M-P ratios varied inversely with the severity of the obstructive process, i.e., the more severely obstructed patients had a fall in Vmax after a deep inhalation (DI). By contrast, equally severe obstruction acutely induced in subjects with mild asthma was associated with an increase in Vmax after a DI. There was no difference between the spontaneous versus the induced groups in degree of nonhomogeneity as assessed by single-breath nitrogen tests. Changes in specific airway conductance after a DI during spontaneous obstruction were in the same direction as the changes in Vmax, and the time course for restitution of airway caliber in subjects who showed bronchoconstriction after a DI was significantly longer than for those subjects who showed bronchodilatation. We conclude that in severe bronchial asthma with spontaneous obstruction, a DI produces an increase in severity that is opposite to the results found in acutely induced obstruction, and the time course for reestablishing baseline airway caliber is more prolonged. We suggest that mechanisms for and sites of obstruction vary between the 2 groups.

Dutch workers have proposed that people with asthma and those smokers who develop chronic airflow obstruction share a common allergic constitution. To study whether smoking itself is associated with indicators of allergy, we have examined 237 men aged 51-61 years (120 smokers, 73 ex-smokers, and 44 non-smokers) who were recruited to a long term study of lung function in 1974, at which time men with a clinical diagnosis of asthma were excluded. Smokers, ex-smokers, and non-smokers did not differ in personal or family history of allergic disease, but the prevalence of positive responses to skinprick tests was greater in ex-smokers (59%) than in the other two groups (33% and 34%). In men with negative responses to skinprick tests total serum IgE was greater in smokers (log10 mean 1.41 IU/ml) and in ex-smokers (log10 mean 1.53 IU/ml) than in non-smokers (log10 mean 1.12 IU/ml). In men with positive skin test responses serum IgE was similar in the three groups (log10 mean ranging from 1.68 to 1.78 IU/ml). Geometric mean total white cell counts in the peripheral blood were higher in smokers (7.34 X 10(9)/l) than in non-smokers (5.82 X 10(9)/l); the value in ex-smokers (6.16 X 10(9)/l) was intermediate. Absolute blood eosinophil counts were increased in smokers disproportionately to the increase in total white cell count. Thus smoking is associated with small increases in some markers of allergy. These changes are probably acquired after the onset of smoking but sequential studies are required to amplify these cross sectional observations. Smokers whose skin test responses are positive appear more likely to give up smoking.

Pulmonary and airway mechanics were assessed in seven asthmatic patients in remission, when asthma was induced by exercise and again after spontaneous recovery or bronchodilator treatment. After exercise there was a sustained fall in forced expiratory volume in 1 s (FEV 1.0) in all patients, varying from 30 to 80 percent of the initial value. Total lung capacity (TLC) increased significantly in four of the seven patients. In one of the four patients the increase in TLC was associated with an increase in static transpulmonary pressure at full inflation but in the remaining three patients it was associated with a parallel shift of the pressure-volume curve of the lung without change in its slope. In all patients residual volume increased, regardless of change in TLC; both pressure-volume and maximum expiratory flow-volume curves suggested that widespread airway closure (or virtual closure) occurred at positive transpulmonary pressures when asthma was induced. Loss of lung recoli pressure sometimes contributed to the reduction in maximum expiratory flow but diffuse airway narrowing was probably the dominant abnormality. When air-flow obstruction became more severe the ratio of expiratory to inspiratory time was increased and although expiratory flow limitation was present excessive expiratory pressures were not generated.

Nine patients with bullous emphysema for which surgery was being considered have been investigated with computed tomography (CT). In six out of nine patients (67%) CT showed more extensive disease or bilateral disease where only unilateral was suspected from postero-anterior and lateral chest radiographs. Only one patient proceeded to surgery and post-operative CT showed satisfactory re-expansion of the compressed lung. Surgery was abandoned in one patient as a result of the CT findings. Computed tomography is of value in patients with bullous emphysema in assessing the extent of disease and may assist the surgeon in operative planning.

An overall relation between cigarette smoking and the development of progressive airflow obstruction is established but only a minority of smokers ever develop severe airway narrowing; with the striking but rare exception of homozygous alpha 1-antitrypsin deficiency, the causes of this variation in susceptibility between smokers are uncertain. Possible associated risk factors may be classified under three broad headings--exogenous irritants, broncho-pulmonary infections and endogenous or 'host' factors--and will be briefly reviewed in this paper. But first the natural history of progressive airflow obstruction must be considered because this determines how potential risk factors can be assessed.

Twenty-four patients with reversible airflow obstruction under suboptimal control on conventional therapy entered a double-blind placebo-controlled trial of additional oral sustained release aminophylline. Assessment was by diary cards, twice daily PEFR, and weekly FEV1. Nineteen patients completed the trial satisfactorily. Eleven were improved subjectively by addition of aminophylline. The mean PEFR for all 19 patients rose from 232 1 min-1 SEM +/- 5, to 247 1 min-1 SEM +/- 4 (p less than 0.0001); nine individuals showed a statistically significant improvement in mean PEFR and 10 showed an improvement of greater than 200 ml in their FEV1. Improvement in PEFR on aminophylline was not at the expense of benefit from inhaled salbutamol. Unwanted effects of nausea, headache, and abdominal discomfort were recorded by 12 of the 24 patients entering the trial. Seventeen of the 19 patients completing the trial had plasma theophylline levels in the accepted therapeutic range of 10-20 mg 1(-1). The drug doses required to achieve these levels varied from 8.6-30.8 mg kg-1 24 hr-1 in the patients with no clinical or biochemical evidence of liver disease. Oral aminophylline can improve control of airflow obstruction in patients with moderately severe disease who are already receiving multiple medication, but side-effects often limit its use. The wide dose range required to achieve therapeutic plasma levels indicates that measurements of plasma theophylline are necessary for adequate interpretation of trials of theophylline compounds.

To elucidate the importance of airway closure in limiting maximum expiration, two complementary plethysmographic techniques have been used to estimate the volume of and pressure within the trapped thoracic gas. Three young (19-23 yr) and three older (43-66 yr) subjects were studied. The first study defined the curve of possible pressure-volume relationships for the trapped gas; the second study attempted to estimate the volume of trapped gas. In the first study the subject in a Mead plethysmograph expired through a pneumotachograph and back into the box. A reduction in box volume greater than that caused by drying and cooling of expired gas implies gas compression due mainly to airway closure. In the second study a known volume of air was withdrawn from the mouth at full expiration and changes in box volume and mouth pressure were recorded. The apparent volume in pressure communication with the mouth (Vpc) was calculated using Boyle's law. In the young subjects we did not detect thoracic gas compression although there was evidence of trapped gas (RV-Vpc greater than 0). In the older subjects there was a larger volume of trapped gas that was compressed to pressures of more than 22 cmH2O. Airway closure appears to limit maximal expiration in older subjects.

Pulmonary mechanics and respiratory muscle pressures were studied in 7 patients with severe respiratory muscle weakness. Minimal pleural pressures were grossly abnormal and showed little variation with lung volume. Both the maximal transpulmonary pressure and static expiratory compliance were low; therefore, the pressure-volume curves of the lungs resembled those obtained after strapping the chest in normal subjects. The low compliance may result from either microatelectasis or a generalized alteration in alveolar elastic properties and is probably a major determinant of both the total lung capacity and the breathing pattern of patients with neuromuscular disease. Airway and gas exchange function were less abnormal than the elastic properties of the lungs.

We examined the use of partial expiratory flow-volume (PEFV) curves to obtain dose-response curves to an inhaled beta 2-adrenoceptor agonist (salbutamol) in eight normal subjects. Maximum expiratory flow at low lung volumes increased on both PEFV and full expiratory flow-volume curves, but the increase was always considerably greater on PEFV (28.4%) than on full (14.5%) curves. The percent increase in flow on the PEFV curve was not significantly influenced by the preceding volume history being 90-120 s of tidal breathing, forced expiration to residual volume, or breath holding after a full inflation. These results suggest that normal tone during tidal breathing is temporarily reduced but not abolished by a full inflation, and once basal tone has been restored it is not enhanced by a full expiration. In seven of the eight subjects a satisfactory cumulative dose-response curve to inhaled salbutamol was obtained with a plateau value of maximum flow at a dose of 110 microgram. The relatively good reproducibility of PEFV curves and the considerable bronchodilator signal obtained (29-70% increase in flow above base line in different individuals) suggest that such dose-response curves may be useful in studying normal bronchial pharmacology in vivo.

Ventilation (krypton -81m) and perfusion (technetium -99m) lung scans were obtained in a consecutive series of 21 patients shortly before thoracotomy for proven or suspected carcinoma of the bronchus. In most patients ventilation and perfusion were impaired equally and the scan abnormality corresponded to the bronchoscopic and radiological findings. Unexpectedly large defects in the perfusion scan were seen in three patients, all of whom had extensive neoplastic involvement of the mediastinum at thoracotomy, but 11 other patients had mediastinal involvement which was not suspected from the scan. Ventilation scanning was useful in the prediction of postoperative ventilatory capacity in two patients who underwent pneumonectomy. We conclude that ventilation and perfusion scans are not sensitive indicators of neoplastic involvement of the mediastinum but they are valuable for the prediction of postoperative lung function.

Airway occlusion during constant flow inflation allows rapid determination of frequency-dependence of pulmonary resistance by estimating its extreme values: RL,max (zero frequency) and RL,min (high frequency). RL,max represents the maximum resistance value that can be obtained with the prevailing time constant inequalities and stress relaxation, while RL,min represents the resistance that would be obtained in the absence of time constant inequalities and stress relaxation. In 5 anesthetized, tracheostomized, paralyzed, and artificially ventilated cats, RL,min, RL,max, and static pulmonary elastance (EL,st) have been measured following airway occlusion at the end of constant flow tidal inflations. Measurements were made before and during continuous infusion of increasing doses of serotonin (10-100 micrograms/kg/min IV). The development of intrinsic positive end-expiratory pressure (PEEPi) was also assessed. Cats varied greatly in their responsiveness to serotonin, but RL,min, RL,max, and EL,st increased and PEEPi developed in all cats. Increases in RL,max did not always parallel increases in RL,min but were similar to those in EL,st, suggesting that altered viscoelastic properties of the lung contributed to the increases in RL,max. We conclude that time-constant inequalities, changes in the lung periphery, and hyperinflation probably all contribute to the observed increases in RL,max and will influence conventional methods of measuring RL. Measuring RL,min potentially provides a better method for assessing the reduction in caliber of the conducting airways in isolation.