Regional distribution of pulmonary ventilation and perfusion in elderly subjects.

Using radioactive xenon, we measured the regional distribution of pulmonary ventilation and blood flow in six normal men, whose ages ranged between 65 and 75 yr. The measurements were made in the standing position. The static volume-pressure relation of the lungs was also measured in five of the subjects. The results indicate that by comparison with normal young men: (a) Blood flow to the upper lung zones was increased, although it still remained predominant in the lower zones. (b) Ventilation distribution during a vital capacity inspiration was similar to that seen in young subjects. (c) In five of the six elderly subjects, however, the distribution of ventilation in the resting tidal volume range was not preferential to the lower zones as it was in young men. This was probably caused by airway closure in the lower lung zones. The elderly subjects thus exhibit during normal tidal volume breathing a ventilation distribution pattern similar to that observed in young subjects when breathing at low lung volumes, i.e., near residual volume. This difference is probably due to the combined effect of the loss in elastic recoil of the lungs observed in the elderly subjects and of a decreased resistance to collapse of the aged airways. These findings suggest that in the elderly subjects there is a significant regional ventilation-perfusion impairment during quiet breathing, which may explain in part the reported increase in alveolar-arterial oxygen difference with advancing age.

Regional distribution of pulmonary ventilation and perfusion in obesity.

Five women and three men, all obese and weighing 95 to 140 kg, were studied by routine pulmonary function tests and by a radioactive xenon technique, while seated upright at rest, to measure the regional ventilation and perfusion distribution in the lung. In four subjects in whom the expiratory reserve volume averaged 49% of predicted normal, the ventilation distribution as measured with (133)xenon was normal. In the remaining four subjects, in whom the expiratory reserve volume was reduced to less than 0.4 L and averaged only 21% of predicted values, the distribution of a normal tidal breath was predominantly to the upper zones. In all subjects the perfusion distribution was predominantly to the lower lung zones but was slightly more uniform than in normal nonobese subjects. During tidal-volume breathing, therefore, in four subjects the ventilation and perfusion distribution was substantially normal, whereas in the remaining four perfusion was maximal in the lower zones, to which ventilation was significantly reduced. These findings show that there may be significant ventilation/perfusion abnormality on a regional basis in obese subjects, this abnormality bearing a close relationship to the reduction in expiratory reserve volume, a finding predictable from recently published data on normal nonobese subjects (1). The abnormalities of ventilation/perfusion relationships that were demonstrated in four of the eight obese subjects could cause a reduction in arterial oxygen tension during resting tidal ventilation.

Regional lung function in patients with bronchial asthma.

The regional distribution of pulmonary ventilation and perfusion and regional alveolar ventilation/perfusion ratios were measured with radioactive xenon ((133)xenon) in 10 patients with asthma in remission. Four subjects had normal ventilation distribution, four had hypoventilation in some regions and normal ventilation in others, and two patients had abnormal ventilation in almost all lung regions. The lung bases were involved most frequently and the middle zones least frequently. Correlation was good between the degree of over-all ventilatory impairment calculated from (133)xenon values and measurement of the maximal midexpiratory flow rate the same day. Regions which were hypoventilated had low ventilation/perfusion ratios and also tended to be hypoperfused. In the eight subjects who had been studied similarly 5 yr previously, changes in regional function correlated in general with changes in over-all function.

Detection of chronic respiratory bronchiolitis in oxidant-exposed populations: analogy to tobacco smoke exposure.

Studies in nonhuman primates indicate that one pathophysiologic consequence of ozone exposure is chronic bronchiolitis in terminal bronchioles. Modeling dosimetry suggests that a similar phenomenon is possible in humans. These findings may constitute an important analogy to the respiratory bronchiolitis that is associated with tobacco smoking in young adults. This analogy could form the basis for future research related to chronic respiratory health effects of ozone. The smoking data are reviewed and several research strategies are proposed that will be developed more fully in subsequent articles in this volume.

Lines that connect: assessing the causality inference in the case of particulate pollution.

The question of when it would be appropriate to conclude that the associations between particulate pollution and various outcomes (including mortality) should be judged as causal in nature has been difficult and controversial. Although such a judgment must be subject to revision, the volume of new information and new experimental findings has been so great that such a reevaluation is required at frequent intervals. The useful summary by Gamble [PM(2. 5) and Mortality in Long-Term Prospective Cohort Studies: Cause-Effect or Statistical Associations? Environ Health Perspect 106:535-554 (1998)] of the reasons why a causal inference was, in his opinion, not justified provides a basis for reevaluation in the light of new data. Such a reexamination indicates that the associative evidence is now stronger and that the biologic basis for a number of adverse effects has now been demonstrated. All of the useful guideline criteria customarily applied to such questions seem to have been met, although there is still much to be learned about interactive effects and the possibility of statistical thresholds.

Observations on asthma.

A review of the present understanding of asthma leads to the following conclusions: an elevated IgE is the principal risk factor in the development of childhood asthma; secondary exposure to a wide range of environmental agents (including indoor bioallergens) accounts for the variations in prevalence; prevalence (defined by a positive answer to the question "Have you ever had doctor-diagnosed asthma?") ranges between 4 and 8% in children. Black children have a slightly higher prevalence than white children in the United States, and in both races boys have a higher prevalence than girls. A high prevalence is found in Puerto Rican children in the United States. Patterns of utilization of health care resources (hospital emergency departments, individual physicians, etc.) are dependent on economic circumstances. Low-income children have higher annual morbidity (days in hospital, days off school, etc.) than higher income children and are more dependent on hospital emergency departments for primary care. Relatively little is known about nonatopic asthma in adults, although virus infections and occupational exposures play some part in its induction. There are some striking examples of asthma attack periodicity, and much may be learned from these. Hospital admissions for asthma have increased in many regions over the past 15 years; it is unlikely that this represents the increased admission of milder cases and hence would indicate that asthma has become more severe. This is likely to be a more sensitive indicator of change than mortality. Associations between indices of health effects and air pollutants indicate that these are probably playing a role in the worsening of asthma. Adverse effects related to SO2 and NO2 exposures have been documented, and fine particulate pollution (PM10) is also associated with worsening of asthma. Ozone is an intense respiratory irritant, and, together with acid aerosols, may well be playing a role in the worsening of asthma. It is not known whether any of these agents are affecting prevalence.

The effects of air pollution on children.

Air pollutants have been documented to be associated with a wide variety of adverse health impacts in children. These include increases in mortality in very severe episodes; an increased risk of perineonatal mortality in regions of higher pollution, and an increased general rate of mortality in children; increased acute respiratory disease morbidity; aggravation of asthma, as shown by increased hospital emergency visits or admissions as well as in longitudinal panel studies; increased prevalence of respiratory symptoms in children, and infectious episodes of longer duration; lowered lung function in children when pollutants increase; lowered lung function in more polluted regions; increased sickness rates as indicated by kindergarten and school absences; the adverse effects of inhaled lead from automobile exhaust. These impacts are especially severe when high levels of outdoor pollution (usually from uncontrolled coal burning) are combined with high levels of indoor pollution. In developed countries, where indoor pollution levels are lower, increasing traffic density and elevated NO2 levels with secondary photochemical and fine particulate pollution appear to be the main contemporary problem. By virtue of physical activity out of doors when pollution levels may be high, children may experience higher exposures than adults. Air pollution is likely to have a greater impact on asthmatic children if they are without access to routine medical care.

Epidemiologic basis for photochemical oxidant standard.

The problem of photochemical oxidant pollution, 98% of which is ozone, is addressed. Ozone itself is not the cause of all adverse effects (e.g., peroxyacetyl nitrites cause eye irritation). The typical sequence in the development of oxidant pollution is an initial increase in nitrous oxide, followed by nitrogen dioxide, followed by ozone. These pollutants can be carried long distances and may have long range effects. Ozone is considered by far the most irritant gas to humans, with effects seen even at extremely low concentrations. Dr. Bates reviewed the initial results of a study of hospitalization in the Niagara Peninsula of Ontario as it related to hourly pollution measurement, noting a relationship between elevated ozone and SO2 levels and respiratory admissions within 24 hr during the summer months. This is an important preliminary finding, as EPA data indicate that nitrogen oxides are increasing while other pollutants are decreasing.

The Ontario Air Pollution Study: identification of the causative agent.

Previously published data from the Ontario Air Pollution study are reviewed. It has been shown that there is a consistent association in summer between hospital admissions for respiratory disease in Southern Ontario, and daily levels of SO4, O3, and temperature. No association exists for a group nonrespiratory conditions. Multiple regression analyses are presented that show all environmental variables account for 5.6% of the variability in respiratory admissions and that if temperature is forced into the analysis first, it accounts for 0.89% of the variability only. Distribution plots of standardized residuals are presented. In June of 1983, there were an exceptional number of ozone episodes (defined as occasions when ozone was greater than 82 ppb for 3 or more hours in a calendar day) in this region. A separate analysis of hospital admissions for acute respiratory diseases for the month of June for several years shows no demonstrable excess in June of 1983; previously regional analyses have indicated that ozone is associated with increased levels in July and August over a 9-year period. It has also been found that daily SO4 data collected at one monitoring site in the center of the region are not correlated with respiratory admissions, whereas the SO4 values collected every sixth day, on different days of the week, at 17 stations in the region had the highest correlation with respiratory admissions.(ABSTRACT TRUNCATED AT 250 WORDS)

Health effects of particulate air pollution: time for reassessment?

Numerous studies have observed health effects of particulate air pollution. Compared to early studies that focused on severe air pollution episodes, recent studies are more relevant to understanding health effects of pollution at levels common to contemporary cities in the developed world. We review recent epidemiologic studies that evaluated health effects of particulate air pollution and conclude that respirable particulate air pollution is likely an important contributing factor to respiratory disease. Observed health effects include increased respiratory symptoms, decreased lung function, increased hospitalizations and other health care visits for respiratory and cardiovascular disease, increased respiratory morbidity as measured by absenteeism from work or school or other restrictions in activity, and increased cardiopulmonary disease mortality. These health effects are observed at levels common to many U.S. cities including levels below current U.S. National Ambient Air Quality Standards for particulate air pollution.

Mechanism of action of ozone on the human lung.

Fourteen healthy normal volunteers were randomly exposed to air and 0.5 ppm of ozone (O3) in a controlled exposure chamber for a 2-h period during which 15 min of treadmill exercise sufficient to produce a ventilation of approximately 40 l/min was alternated with 15-min rest periods. Before testing an esophageal balloon was inserted, and lung volumes, flow rates, maximal inspiratory (at residual volume and functional residual capacity) and expiratory (at total lung capacity and functional residual capacity) mouth pressures, and pulmonary mechanics (static and dynamic compliance and airway resistance) were measured before and immediately after the exposure period. After the postexposure measurements had been completed, the subjects inhaled an aerosol of 20% lidocaine until response to citric acid aerosol inhalation was abolished. All of the measurements were immediately repeated. We found that the O3 exposure 1) induced a significant mean decrement of 17.8% in vital capacity (this change was the result of a marked fall in inspiratory capacity without significant increase in residual volume), 2) significantly increased mean airway resistance and specific airway resistance but did not change dynamic or static pulmonary compliance or viscous or elastic work, 3) significantly reduced maximal transpulmonary pressure (by 19%) but produced no changes in inspiratory or expiratory maximal mouth pressures, and 4) significantly increased respiratory rate (in 5 subjects by more than 6 breaths/min) and decreased tidal volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Historical review: the carbon monoxide diffusing capacity (DLCO) and its membrane (DM) and red cell (Theta.Vc) components.

The single breath carbon monoxide diffusing capacity (DLCO sb), also called the transfer factor (TLCO), was introduced by Marie and August Krogh in two papers (Krogh and Krogh, Skand. Arch. Physiol. 23, 236-247, 1909; Krogh, J. Physiol., Lond. 49, 271-296, 1915). Physiologically, their measurements showed that sufficient oxygen (by extrapolation from CO) diffused passively from gas to blood without the need to postulate oxygen secretion, a popular theory at the time. Their DLCO sb technique was neglected until the advent of the infra-red CO meter in the 1950s. Ogilvie et al., J. Clin. Invest. 36, 1-17, 1957 published a standardized technique for a 'modified Krogh' single breath DLCO, which eventually became the method of choice in pulmonary function laboratories. The Roughton-Forster equation (J. Appl. Physiol. 1957, 11, 290-302) was an important step conceptually; it partitioned alveolar-capillary diffusion of oxygen (O2) and carbon monoxide (CO) into a membrane component (DM) and a red cell component (theta.Vc) where theta is the DLCO (or DL(O2)) per ml of blood (measured in vitro), and Vc is the pulmonary capillary volume. This equation was based on the kinetics of O2 and CO with haemoglobin (Hb) in solution and with whole blood Hartridge and Roughton, Nature, 1923, 111, 325-326; Proc. R. Soc. Lond. Ser. A, 1923, 104, 376-394; (Proc. R. Soc. Lond. Ser. B, 1923, 94, 336-367; Proc. R. Soc. Lond. Ser. A 1923, 104, 395-430; J. Physiol., Lond. 1927, 62, 232-242; Roughton, Proc. R. Soc. Lond. Ser. B 1932, 111, 1-36) and on the relationship between alveolar P(O2) and 1/DLCO. Subsequently, the relationship between DL(O2) (Lilienthal et al., Am. J. Physiol. 147, 199-216, 1946) and DL(CO) was defined. More recently, the measurement of the nitric oxide diffusing capacity (DLNO) has been introduced. For DL(O2) and DLNO the membrane component (as 1/DM) is an important part of the overall diffusion (transfer) resistance. For the DLCO, 1/theta.Vc probably plays the greater role as the rate limiting step. A crucial question, the effect of unstirred plasma layers on the 'true' value of thetaCO in vivo, has not been resolved, but this does not detract from the clinical role of the DLCO sb (TLCO) as an essential test of lung function.

Adverse health impacts of air pollution--continuing problems.

Evidence has been published that current levels of fine particulate pollution are associated with a wide range of adverse health outcomes, including accelerated mortality. Tropospheric ozone, often in association with aerosol sulfates, is similarly and independently associated with increased emergency visits and hospital admissions for acute respiratory disease, and there are sound reasons for suspecting that asthma may be worsened by exposure to it. Whether nitrogen dioxide is important at current levels in inducing adverse health effects is unclear. Although the combination of sulfur dioxide and particulate pollution that results from uncontrolled coal burning has been known for 30 years to be harmful, the independent role of sulfur dioxide cannot yet be precisely defined. A first report has appeared that ambient levels of volatile organic compounds may be associated with symptoms. Current efforts to assess the costs, in economic terms, of the adverse health effects attributable to air pollution are likely to be intensified.

Revisiting "respiratory function in emphysema in relation to prognosis".

BACKGROUND: The 1956 paper by DV Bates, JMS Knott and RV Christie, "Respiratory function in emphysema in relation to prognosis" Quart J Med 1956;97:137-157 is largely reprinted with a commentary by the first author, Dr David Bates. Although the pathology of emphysema was well recognized at the time, the clinical diagnosis and assessment of its severity were known to be imprecise; physiological measurements assessing and following the clinical course had not been established. The study aimed to follow systematically a group of patients, selected by clinical criteria using standardized clinical and physiological techniques, over four years and correlate physiological and clinical changes in relation to prognosis and eventually to postmortem findings. Fifty-nine patients were recruited to an emphysema clinic at St Bartholomew's Hospital, London, England. Inclusion criteria were dyspnea without other causes and no cor pulmonale present. Patients' symptoms were assessed by a standardized questionnaire, and measurements were taken of lung volumes, maximal ventilatory volume, carbon monoxide diffusing capacity at rest, exercise and oxygen saturation by oximetry. During the four years of the study, 17 patients died (actuarial expected - four) and 13 presented with signs of pulmonary heart failure. All postmortem examinations (n=9) showed advanced emphysema. A seasonal variation in dyspnea was established (the period included the infamous 1952 London smog). Four patients improved, and the remainder were unchanged or deteriorated. Close relationships were shown between dyspnea and function results, particularly for the diffusing capacity of lungs for carbon monoxide (DLCO). A comparison among a group of patients with chronic bronchitis without dyspnea showed that the DLCO discriminated between them. A loss of the normal increase in DLCO during exercise was shown in emphysema. IMPORTANCE: The study showed the value of standardized clinical and physiological techniques in following chronic obstructive pulmonary disease patients, and of separating the effects of airflow obstruction from impaired gas exchange function. Impaired gas exchange was shown to be important in influencing prognosis.

Effects of ozone exposure in Canadians and Southern Californians. Evidence for adaptation?

Comparison of published reports on physiological effects of exposure to ozone (O3) suggests that Canadians are more reactive than southern Californians. Responses of subjects and experimental methods were compared in a cooperative investigation of this apparent difference in reactivity. Four Canadians and four Californians were exposed to 0.37 ppm O3 in purified air at 21 degrees C and 50% relative humidity for 2 hours with intermittent light exercise. Exposures to purified air alone served as controls. Responses of subjects were similar to those observed previously: Canadians on the average showed greater clinical and physiological reactivity to exposure than did Californians, who were no more than minimally reactive. Canadians also showed larger increases in erythrocyte fragility following exposure. No methodological differences sufficient to explain different results of previous studies were found. Although other possible explanations have not been ruled out entirely, adaptation of southern Californians to chronic ambient O3 exposure is a rational hypothesis to explain these results.