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We describe the natural history of cryptogenic bronchiolitis obliterans in a patient followed for 24 yrs with serial pulmonary function tests and radiology. Severe, progressive airway obstruction developed, with overinflation but preservation of KCO. There was progressive hypoxaemia, which worsened on exertion; hypercapnoea was modest until late in the illness. Neither bronchodilators nor steroids were effective. The chest radiograph remained normal; CT showed irregular areas of low attenuation peripherally throughout the lungs, with Hounsfield numbers typical of emphysema, but no bullae. Postmortem studies included histology and quantitative studies of a corrosion cast of one lung. They showed marked airway narrowing at all levels, with pruning of peripheral branches, mucus plugging, and some emphysema. The case illustrates that cryptogenic bronchiolitis obliterans may be chronic and difficult to distinguish clinically or by investigation from other forms of chronic obstructive airways disease, particularly emphysema.

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Studies of bronchial tree data by West et al. (J. Appl. Physiol. 60: 1089-1097, 1986) have shown that plots of mean diameter against generation, using log-log scales, can be represented by a power function with harmonic modulations. Other studies have shown that the mean diameter of the airways is exponentially related to order of branching. This paper demonstrates that both observations are compatible with a fractal model of branching, and because airway branching is fractal, this may explain why both are also true of the bronchial tree. Furthermore, the exponential relationship of mean diameter with generation in the larger airways, demonstrated by Weibel, is shown to result from the exponential relation of diameter with order in the fractal model.

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A case of recurrent pleural pain without pneumothorax, thought to be due to pulmonary endometriosis, is presented. The pain was associated with the menstrual periods, remitted when the patient was sterilised, recurred when she was given oestrogens, and finally disappeared when the oestrogen was stopped. The presentation of pulmonary endometriosis, with pleural pain but no pneumothorax, should be added to those previously described in the literature.

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Measurements were made of the diameters of the three branches meeting at each of 1,937 bifurcations in the pulmonary arterial tree, using resin casts from two fully inflated human lungs. Cross-sectional areas of the parent branch and of the daughter branches were calculated and plotted on a log-log plot, which showed that mean cross-sectional area increases in a constant proportion of 1.0879 at bifurcations. The mean value of the ratio of daughter branch diameters at bifurcations was 0.7849. The mean value of the exponent z in the equation flow = k (diameter(z)) was found to be 2.3 +/- 0.1, which is equal to the optimal value for minimizing power and metabolic costs for fully developed turbulent flow. Although Reynolds number may exceed 2,000 in the larger branches of the pulmonary artery, turbulent flow probably does not occur, and in the peripheral branches Reynolds number is always low, excluding turbulent flow in these branches. This finding seems to be incompatible with the observed value of z. A possible explanation may be that other factors may need to be taken into account when calculating the theoretical optimum value of z for minimum power dissipation, such as the relatively short branches and the disturbances of flow occurring at bifurcations. Alternatively, higher arterial diameters reduce acceleration of the blood during systole, reduce turbulent flow, and increase the reservoir function of the larger arteries. These higher diameters result in a lower value of z.

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There are few reports of long term follow up of symptoms in firemen. In a four year study of symptoms in a group of 96 firemen (31 non-smokers, 40 smokers, and 25 ex-smokers) of which 89 remained in the study for its full duration a volunteer control group of 69 male non-smokers from a variety of occupations was also followed up. A history of symptoms and of smoking habits was obtained on entry to the study, then every six months for two years, and annually for a further two years. All those remaining in the study after four years were interviewed and a history of their use of breathing apparatus and of being affected by smoke and fumes was obtained. Symptom frequency was least in control subjects, intermediate in non-smokers and ex-smokers, and most in smokers. Before the study period (history obtained at the first session) smoking increased symptoms 3.9 times and being affected by smoke in the past increased symptoms 2.3 times, compared with non-smokers who had not been affected by smoke. In smokers who had also been affected by smoke symptoms increased by 9.1 times, suggesting a multiplicative effect. During the study period symptom frequency was increased about 4.4 times in smokers and 5.7 times in those who had been affected by smoke at work in the past compared with non-smokers who had not been affected by smoke. In smokers who had also been affected by smoke symptom frequency increased by 7.4 times, the combined effects of the two types of smoker being less than additive. These results suggest that being affected by smoke and fumes at work may be a cause of long term symptoms in firemen. In firemen who are non-smokers and who had not been affected by smoke symptom frequency was similar to that observed in the control subjects. Thus the current routine use of breathing apparatus appears to be effective in preventing long term symptoms.

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1. Pulmonary function tests, including alveolar mixing efficiency by the single-breath and multi-breath methods, and ventilation scans were performed on 16 volunteer subjects. The tests were repeated after the inhalation of a methacholine aerosol in sufficient dosage to increase airways resistance. 2. After inhalation of methacholine there was a significant fall in mean series dead space of 31 ml (P less than 0.05), and mean multi-breath alveolar mixing efficiency fell from 68% to 36% (P less than 0.001), a fall occurring in all subjects. Mean single-breath alveolar mixing efficiency measured on the first breath of the nitrogen washout fell from 76% to 70%, but this change did not reach statistical significance (0.1 greater than P greater than 0.05). 3. In eight of the subjects, technically adequate lung scans and pulmonary function tests were obtained both before and not more than 30 min after methacholine inhalation. In seven there were obvious visible defects on the ventilation scans, and in five of these the computer-calculated underventilation score became abnormal. 4. Thus inhalation of methacholine causes maldistribution of ventilation, a fall in alveolar mixing efficiency and a fall in series dead space, presumably brought about by bronchoconstriction. The parallel component of this maldistribution of ventilation, as judged by 81mKr ventilation scanning, does not of itself seem to be sufficient to explain the fall in alveolar mixing efficiency, and therefore a degree of diffusion limitation is probably involved as well.

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Although firefighting is a hazardous occupation, published evidence of long-term lung damage in firemen is inconsistent. A group of 96 men from the West Sussex Fire Brigade, which covers a simi-rural, semi-urban area, were followed up for between one and four years. They included 31 non-smokers, 40 smokers, and 25 ex-smokers. After four years 12 firemen had been lost to the study. A control group of 69 volunteers, consisting of non-smoking men from various other occupations, were followed up in parallel. Lung function tests, covering a wider range than has been previously used in similar studies, were repeated six monthly for two years and annually for a further two years. The results were expressed in terms of the rate of change with time of the lung function variables. Many of the variables deteriorated in both firemen and controls, but the rate of deterioration was greater in the controls than the firemen for vital capacity, ratio of residual volume to total lung capacity, FEV1, FVC, peak expiratory flow (PEF), flow at 50% and 25% remaining vital capacity (V50 and V25 respectively), and airways resistance (Raw). With respect to PEF, V50, V25, and Raw the control subjects deteriorated more rapidly even than the smokers and ex-smokers among the firemen. Alveolar mixing efficiency (AME), a measure of small airways function, did not change significantly over the study period in any group. Non-smoking firemen had the highest mean value of AME, decreasing through ex-smokers, controls, and smokers. We conclude that these results show no evidence of chronic lung damage in West Sussex firemen; indeed, the firemen as a group show a lower rate of deterioration of lung function with age than do the control subjects. This is attributed to the selection of fit men for the service, continued physical training, and the regular use of breathing apparatus.

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Bronchial tree casts were made from one or both lungs from nine children aged from five weeks to 17 years. The branches of the casts were ordered by the method of Strahler, and diameter ratio, length ratio, and branching ratio were determined. From five to 12 weeks the diameter ratio is about 1.35, but by 13 months it has risen to 1.45, indicating a faster rate of growth in the larger airways over the period; thereafter it stays at or above this level. The data show that the peripheral conducting airways are relatively large in diameter at 1-3 months, attaining their adult proportion after one year. In contrast, length ratio shows no trend with age. On the assumption of 25,000 terminal bronchioles, the mean number of orders between terminal bronchiole and trachea was estimated to be about 12.

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Triple resin casts were made of the pulmonary arteries, veins, and airways from six dog lungs. The airways were cast at a pressure of 25 cm resin in all six. In the first three, both vessels were cast at a pressure of 30 cm resin, and in the second three, arteries were at 10 cm resin and veins at 5 cm resin. Measurements were made of luminal airway diameters down to 1 mm and of the luminal diameters of the corresponding segments of the vascular trees. The relation of one to the other was shown by calculating the regression lines for the corresponding diameters. Intrapulmonary arteries and veins are of approximately equal diameter when cast at 30 cm resin, while the veins are 20% larger than the arteries when cast at 5 cm and 10 cm of resin, respectively. Both vessel diameters are 75% of bronchial at the higher pressure, while at the lower pressures arteries are 59%, and veins 71% of bronchial. In any individual, vessel diameters are a relatively constant proportion of airway diameter. This constant of proportionality varies considerably between dogs, its value ranging from 0.48 to 1.03. It is concluded that in any individual all three trees have similar diameter ratios--that is, the ratio between mean diameters of branches in successive orders.

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The literature has suggested that branching angles depend on some principle of optimality. Most often cited are the minimization of lumen surface, volume, power and drag. The predicted angles depend on the principle applied, chi and alpha. Assuming flow o r chi, chi can be determined from r chi 0 = r chi 1 + r chi 2 when the radii of the parent (r0) major (r1) and minor (r2) daughters are known. The term alpha = r2/r1. Using different values for chi and alpha, we present graphs for the major and minor branching angles theta 1 and theta 2 and psi = theta 1 + theta 2 for each of the four optimization principles. Because psi is almost independent of alpha for values of chi and alpha found in 198 junctions taken from a human pulmonary artery, we are able to produce a plot of psi versus chi for each of the four principles on one graph. A junction can be provisionally classified as optimizing for a given principle if, knowing chi, the psi obs - psi pred is least for that principle. We find that this nomographic classification agrees almost perfectly with a previous classification based on a more exacting measure, the percent cost index I, where I = observed cost/minimum cost. We explain why this is to be expected in most but not all cases. First we generate a contoured percent cost surface of c = I - 100 around the optimally located junction, J, and superimpose a surface of equal angular deviations a = psi pred-psi obs. We find that c increases and a usually increases with distance from J as the actual junction moves along a straight line away from J. We then produce a plot of c versus a for two competing principles. A comparison of the principles demonstrates that, for most cases, a is smaller for the principle which has the smaller c value.

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Many kinds of naturally occurring trees have been the subject of study by investigators from a wide variety of disciplines, employing different techniques each with its own advantages and disadvantages. In this paper two such techniques for studying trees are compared: one is the classification of branches by order and the calculation of the branching ratio; the other is vertex analysis. The two methods, which at first sight appear different, are found to be mathematically similar. In complete trees, much the same information can be obtained from counting branches in each order as can be obtained from vertex analysis. In the case of pruned trees, overall branching ratio may give the more consistent results.

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Dichotomously branching trees were generated by computer using random terminal and random segmental growth. The branching ratio (Rb) of such a tree during growth oscillates periodically as new branches are added. The magnitude of the oscillations diminishes as the tree enlarges and Rb converges towards an expected value. This phenomenon was investigated using the reverse of the growth process, that is by terminal or segmental subtraction of branches from existing trees. These were either computer generated trees or mammalian bronchial tree data. The oscillations of Rb thus obtained were similar to those obtained during growth and were used to calculate convergent values of Rb. In addition, an estimate of convergent Rb was obtained from the mean of the maximum and minimum Rb of the first oscillation occurring when the least number of branches had been subtracted. Values of Rb obtained by these methods were compared with those obtained by taking the antilogarithm of the slope of the regression of log number of branches against order. With large trees the results are similar, but with smaller trees a more reliable Rb is given by the means of the oscillations. We find that Rb values from the bronchial trees are different from those generated by random segmental growth and are not always in good agreement with random terminal growth. Some other growth process must therefore be operative in the bronchial tree.

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A model of the pulmonary airways was used to study three single-breath indices of gas mixing, dead space (VD), slope of the alveolar plateau, and alveolar mixing inefficiency (AMI). In the model, discrete elements of airway volume were represented by nodes. Using a finite difference technique the differential equation for simultaneous convection and diffusion was solved for the nodal network. Conducting airways and respiratory bronchioles were modeled symmetrically, but alveolar ducts asymmetrically, permitting interaction between convection and diffusion. VD, alveolar slope, and AMI increased with increasing flow. Similar trends were seen with inspired volume, although slope decreased at high inspired volumes with constant flow. VD was affected most by inspiratory flow and AMI and alveolar slope by expiratory time. VD fell approximately exponentially with time of breath holding. Eight different breathing patterns were compared. They had a small effect on alveolar slope and AMI and a greater effect on VD. The model shows how series and parallel inhomogeneity occur together and interact in asymmetrical systems: the old argument as to which is the more important should be abandoned.

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The first four breaths from a multi-breath nitrogen wash-out have been analysed in 20 normal subjects by differentiation and data smoothing of phase II of the expired concentrations of nitrogen and carbon dioxide. This procedure yields a distribution curve which is skewed to the right, the mode of which represents the usual value of dead space. The minimum and maximum values were found by excluding 2.5% of data points at each end of the distribution. The values of minimum, mode and maximum in men were 67.6, 147 and 300 ml. For women the values were 55.4, 109 and 235 ml. It is suggested that this distribution reflects the asymmetrical nature of the bronchial tree and comparison with anatomical data suggests that anatomy is the principal determinant of the distribution of dead space. The contribution made by the spread of the stationary interface within individual bronchioles is evident but small.

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Morphometric studies of pulmonary airways and arteries can be laborious and time consuming. In order to see whether the effort involved could be reduced in some cases, data obtained from axial pathways of bronchopulmonary segments or lobes were compared with the mean total data obtained from four lungs. It was concluded that axial pathway data classified by generations could be compared between lungs only if the same segment or lobe was used from each individual. Such data are usually not representative of the total structure. Data from axial pathways of segments or lobes which have been classified by Horsfield orders can be pooled, and the mean values thus obtained are fairly close to the mean values obtained from the total data.

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This paper presents an exact analytical solution to the problem of locating the junction point between three branches so that the sum of the total costs of the branches is minimized. When the cost per unit length of each branch is known the angles between each pair of branches can be deduced following reasoning first introduced to biology by Murray. Assuming the outer ends of each branch are fixed, the location of the junction and the length of each branch are then deduced using plane geometry and trigonometry. The model has applications in determining the optimal cost of a branch or branches at a junction. Comparing the optimal to the actual cost of a junction is a new way to compare cost models for goodness of fit to actual junction geometry. It is an unambiguous measure and is superior to comparing observed and optimal angles between each daughter and the parent branch. We present data for 199 junctions in the pulmonary arteries of two human lungs. For the branches at each junction we calculated the best fitting value of x from the relationship that flow alpha (radius)x. We found that the value of x determined whether a junction was best fitted by a surface, volume, drag or power minimization model. While economy of explanation casts doubt that four models operate simultaneously, we found that optimality may still operate, since the angle to the major daughter is less than the angle to the minor daughter. Perhaps optimality combined with a space filling branching pattern governs the branching geometry of the pulmonary artery.

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In nine anesthetized and ventilated dogs heart block was induced at thoracotomy, a pacemaker was inserted, and an electromagnetic flow transducer was placed round the main pulmonary artery. The chest was then closed. Stroke volume (SV) was varied by changing central blood volume. Ventilatory dead space (VDS) and alveolar nitrogen mixing efficiency (ANME) were measured at three levels of heart rate (HR) and three levels of SV independently varied during life and also after cessation of heartbeat. Neither VDS nor ANME showed a significant change with HR or SV during life, but mean VDS increased by 43 ml (22%) and mean ANME decreased by 4.4% postmortem. We conclude that cardiac action increases gas mixing at the interface between inspired and resident gas but has only a small effect on gas mixing distal to the interface during respiration without breath holding.

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1. Atropine is known to diminish bronchomotor tone. In order to investigate the acute effect of atropine on respiration and alveolar gas mixing, a dose of 2.4 mg was given intravenously. 2. Ten normal male volunteers were each studied three times with a nitrogen washout method, once before administration of atropine and then 20 min and 60 min thereafter. 3. After the administration of atropine there was a reduction in tidal volume, a slight increase in frequency of respiration and an increase in series dead space. The tidal mixing volume showed a fall of 25%. In spite of the reduced alveolar dead space the effective mixing volume fell by 29%. Multi-breath alveolar mixing efficiency fell by 3.5%. 4. Multi-breath alveolar mixing efficiency was found to be less with smaller tidal mixing volumes, a fall of 518 ml in the latter causing a reduction of 17.2% in mixing efficiency. 5. A reduction of 100 ml in tidal volume in normal subjects was associated with a decrease of 6.9% in alveolar mixing efficiency. In the subjects receiving atropine tidal volume reduced by 96 ml, but the observed fall in alveolar mixing efficiency was only 3.5%, This suggests an improvement in alveolar mixing of 3.4% due to the administration of atropine. Despite this small improvement, the mixing efficiency is still only 66%. The residual inefficiency of 34% cannot therefore be explained on the basis of bronchomotor tone.

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