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Small airways in fibrosing alveolitis.

Pulmonary function, including lung elastic recoil, was measured in 9 subjects with fibrosing alveolitis. Closing volume and upstream conductance were studied to assess small airway function. Lung volumes, diffusing capacity, and transfer coefficient were decreased. Peak expiratory flow and the ratio of 1-sec forced expiratory volume to forced vital capacity were normal, whereas total lung resistance was low, suggesting that large airways were not narrowed. Lung elastic recoil was increased, but the changes could be accounted for by the loss of lung volume. Closing volume and closing capacity were increased when expressed as a percentage of vital capacity and total lung capacity, respectively; but again, this could be accounted for by the decrease in lung volume, because the absolute lung volume at which airway closure occurred was normal. Upstream conductance was not reduced. We conclude that there is no evidence of narrowing of functional small airways in ventilated parts of the lung. The mechanical findings are compatible with the patchy involvement seen pathologically in fibrosing alveolitis.

Adult↗

Alterations in lung volume and pulmonary function in relation to hemodynamic changes in acute myocardial infarction.

To characterize the changes in lung volumes after acute myocardial infarction (AMI), and the relationship of these changes to other alterations in lung function which correlate with the severity of pulmonary vascular congestion, we made measurements of pulmonary hemodynamics, lung volume, closing volume, frequency dependence of total pulmonary resistance to forced oscillation, and arterial PO2 in 18 subjects with AMI. The most consistent finding was reduced lung volume which correlated with the severity of pulmonary diastolic hypertension. Frequency dependence of resistance showed a small but significant correlation with pulmonary hemodynamics. Closing volume measurements by the resident gas method in nine subjects was not related to hemodynamics. Follow-up studies at the time of hospital discharge revealed a significant return toward normal for arterial PO2, all lung volumes, and total pulmonary resistance at 9 Hz. Based on measurements in healthy subjects, the reduced lung volume after AMI may explain the changes in resistance. In acute and follow-up studies the degree of lung volume reduction and the severity of hypoxemia were strongly correlated.

Acute Disease↗

Pulmonary function following mild respiratory tract infections ("common cold") in teenagers.

Ventilatory function--forced vital capacity (VC)--forced expiratory volume (in 1-sec forced expiratory flows) static lung volumes, closing volume, and phase III slope (single-breath N2 test) were compared in 94 children with and 436 children without a history of recent mild acute respiratory infection. Their age ranged from 10 to 16 years; subjects with symptoms on the day of the study were excluded. We found no difference in lung function between the two groups, with the exception of a slight (inconsistently significant) increase in closing volume (CV) and the CV/VC ratio. Although the influence of a persistent increase in interstitial lung pressure leading to early small airways closure cannot be ruled out, this isolated functional abnormality probably represents a spurious positive result, arising by chance when a large number of statistical tests are done.

Acute Disease↗

Frequency dependence of total respiratory resistance in early airway disease.

Patients who develop frequency dependence of lung compliance will theoretically have frequency dependence of pulmonary resistance. We investigated the ability of the simpler, noninvasive measurement of frequency dependence of total respiratory resistance to identify subjects with frequency dependence of compliance. Ten healthy nonsmokers, 14 asymptomatic smokers, and 6 patients with obstructive airway disease were studied. Frequency dependence of total respiratory resistance was determined by the superimposed oscillating airflow technique at 3 to 9 cycles per sec, and frequency dependence of lung compliance was determined by measurements at 10 to 80 breaths per min. Spirometry, airway resistance, closing volume, and closing capacity were also measured. Frequency dependence of lung compliance and total respiratory resistance were closely correlated (P less than 0.001, r = 0.82), but closing volume, closing capacity, spirometry, and airway resistance could not be used to identify subjects with abnormal frequency dependence of lung compliance. Measurements of frequency dependence of total respiratory resistance and lung compliance, total respiratory resistance at 3 cycles per sec, and closing volume minus expiratory reserve volume were able to distinguish significantly between the smokers and the nonsmokers, but spirometry, closing volume, closing capacity, and airway resistance could not. These data indicate that in asymptomatic smokers and subjects with obstructive airway disease, frequency dependence of lung compliance can be predicted from measurements of frequency dependence of total respiratory resistance. These two tests appear to have equivalent sensitivity and selectivity in detecting the uneven time constants in the airways of asymptomatic smokers.

Adult↗

The effect of smoking cessation on pulmonary function: a 30-month follow-up of two smoking cessation clinics.

To obtain further information about the effects of cessation of smoking on pulmonary function, we followed subjects who attended 2 smoking cessation clinics during a period of 30 months. This paper reports the results from 15 persons who succeeded in stopping smoking for the full 30-month period and from 42 who did not succeed for more than one month. Testing included a respiratory questionnaire, spirometry, and the single-breath N2 test. Standardized methods, the same equipment, and the same experienced personnel were used throughout the study. We found that forced vital capacity, one-second forced expiratory volume, closing volume as a percentage of vital capacity, closing capacity as a percentage of total lung capacity, and the slope of the alveolar plateau of the single-breath N2 test all improved significantly in the subjects who stopped smoking. This improvement continued for as long as 6 to 8 months, and then remained stable. There was no sex difference in the response to smoking cessation, nor could we find a threshold of function below which cessation did not result in improvement. On the contrary, those subjects with the greatest impairment initially showed the greatest improvement. Respiratory symptoms virtually disappeared in those who stopped smoking. Subjects who continued to smoke showed an initial improvement in some function tests, probably due to a marked decrease in consumption, but no significant improvement during the whole period. We concluded from this study that cessation of smoking results in definite improvement in pulmonary function, that there is greater improvement in persons who begin with impaired function than in those whose function is initially normal, that respiratory symptoms disappear rapidly.

Adult↗

The Basenji-Greyhound dog: antigen-induced changes in lung volumes.

Subdivisions of lung volume, closing volume (CV), pulmonary resistance (RL) and dynamic pulmonary compliance (Cdyn) were measured before and after bronchial challenge with Ascaris suum in seven ascaris-sensitive Basenji-Greyhound (BG) crossbreed dogs. RL increased from a control value of 1.41 +/- 0.43 (mean +/- SE) cm H2O/L/sec to 21.4 +/- 5.15 (P Less Than 0.01) and Cdyn decreased from 163 +/- 32 ml/cm H2O to 43 +/- 11 (P Less Than 0.01) in the first 15 min following ascaris-antigen aerosol (AAA) challenge. Vital capacity (VC) decreased from 1581 +/- 147 ml to 944 +/- 86 (P Less Than 0.005) ml and residual volume (RV) increased from 381 +/- 63 to 577 +/- 68 ml (P Less Than 0.005) following AAA challenge. We conclude that the pulmonary mechanical changes in the BG dog following antigen challenge more closely resemble the changes observed in acute human asthma than do changes occurring in the mongrel dog.

Aerosols↗

Training and oxygen conductance in the elderly. I. The respiratory system.

Static lung volumes, closing volumes and pulmonary diffusing capacity have been measured in a group of 19 subjects (9 M, 10 F) 60 - 76 years old, all volunteers for an exercise training program (nominal 4 hours per week for 11 weeks). Initial static lung volumes were larger than in some previous series, perhaps because our sample was health-conscious and mainly nonsmokers. Training produced no significant changes in any of the pulmonary variables tested, despite a 10% increase of maximum oxygen intake seen in those members of the group who progressed to intensive training (heart rate 145 - 155/min). This reflects the fact that oxygen transport depends more on blood transport than on the respiratory system.

Age Factors↗

The single-breath nitrogen test, mortality, and cancer.

The relationship between indices of the single-breath nitrogen test and mortality, overall cancer incidence, and respiratory cancer incidence was examined in a cohort of 876 men, 46 to 69 yr of age, examined in 1974 and followed until June 1985. Closing volume, closing capacity, and slope of phase III were not related to mortality or cancer. In contrast, FEV1 was related to mortality, with an estimated relative mortality risk of 1.37 (95% confidence interval, 1.11 to 1.70) per liter under the expected FEV1, given height, age, and smoking, but FEV1 was not related to cancer. Inability to perform acceptable single-breath nitrogen test tracings was related to mortality with a relative mortality risk of 2.03 (1.45 to 2.85), but not to cancer. We conclude that indices of the single-breath nitrogen test have no predictive value concerning overall mortality and cancer incidence.

Aged↗

The relationship between symptoms and functional abnormalities in clinically healthy cigarette smokers.

Because a number of "early tests" may now be used to measure abnormalities of lung function in cigarette smokers with normal airflow rates, we evaluated the symptoms of cough, sputum, wheezing, and shortness of breath in 60 nonsmokers and 49 smokers to determine whether these symptoms correlated with measurements of lung function that are believed to be altered by mild obstruction. One or more symptoms were present in 5 per cent of the nonsmokers and 90 per cent of the smokers. Individual symptoms, sums of symptoms (symptoms score), and various combinations of symptoms correlated poorly or not at all to measured values for dynamic lung compliance, closing volume, closing capacity, slope of Phase III, and helium flow-volume curves. The symptoms score correlated negatively (P less than 0.05) with forced maximal expiratory flow at 50 per cent of vital capacity. Inasmuch as the serious consequences of chronic airway obstruction are related to abnormalities of lung function, it is likely the function tests will prove more useful than symptoms to reveal smokers at risk to develop chronic obstructive pulmonary disease. Symptoms cannot be used to detect smokers who are liable to have functional abnormalities suggestive of mild peripheral airway obstruction.

Adult↗

Relationship between the single-breath N test and age, sex, and smoking habit in three North American cities.

This report describes a collaborative study conducted in Montreal, Canada, Portland, Ore., and Winnipeg, Canada, to establish the relationship between the single-breath N2 test and age, sex, and smoking and to determine the prevalence of functional abnormalities in these populations. In nonsmokers, age-related regressions for closing volume, closing capacity, and the slope of phase III obtained from the single-breath N2 test, plus the ratio of the I-s forced expiratory volume to the forced vital capacity had very similar slopes, suggesting that differences in geographic location, climate, air pollution, and occupation had no effect on lung function detectable by these tests. Among the 6 city/six groups there was no systematic difference in the prevalence of functional abnormalities between the cities, but closing capacity expressed as a percentage of total lung capacity was abnormal most often in men and the slope of the alveolar plateau was abnormal most often in women. The prevalence of respiratory symptoms within different smoking categories was similar in the 3 cities. Although the number of cigarettes smoked had a significant effect on every test except the ratio of the I-s forced expiratory volume to forced vital capacity in men, the effect of age was considerably greater than the effect of smoking, and the dose-response relationship was weak. We conclude that additional factors may interact with smoking to place a smoker at risk of developing chronic airflow limitation.

Adult↗

Aging and the respiratory system.

All the components of the respiratory system are affected by aging, though at different rates: i) the lung elastic recoil decreases; ii) PaO2 decreases and the D(A-a)O2 increases; iii) the chest wall becomes stiffer; iv) the inspiratory muscles loose strength; and v) the respiratory centres are less sensitive. Residual volume, closing volume and function residual capacity increase, whereas vital capacity and FEV1 progressively decrease. The flow volume curve becomes more convex to the volume axis at low lung volume. Whether these changes are due to aging or associated with aging is a matter of debate. However, the aging lung is more fragile in the face of respiratory and systemic diseases than the respiratory system of young adults. Nutrition, smoking habits and sleep-related disorders also affect the respiratory system. Although bronchial asthma may also appear in the elderly, chronic obstructive pulmonary disease is one of the most common respiratory diseases in advanced life and is a major cause of respiratory failure and ICU admission. Age in itself is not a risk factor of respiratory failure, but elderly patients have an increased risk of mortality for both acute respiratory failure (the failing lung), and exacerbated chronic ventilatory failure (the failing pump). Although advanced age can influence the final outcome of elderly patients from the intensive care unit (ICU), admission to the ICU as well as the institution of mechanical ventilation should not be denied on the basis of age alone, since the severity of illness, prior health status and admitting diagnosis have more weight than age in the final outcome.

Adult↗

Marijuana smoking, pulmonary function, and lung macrophage oxidant release.

Pulmonary alveolar macrophages lavaged from tobacco smokers release increased levels of oxidants and have been implicated in the pathophysiology of emphysema. It is unknown whether lung macrophages recovered from marijuana smokers also liberate excessive levels of oxidants. To evaluate this possibility, pulmonary alveolar macrophages were obtained by bronchoalveolar lavage from nonsmokers, smokers of marijuana only, smokers of tobacco only, and smokers of tobacco plus marijuana. Spontaneous and stimulated superoxide anion release was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome c. These findings were correlated with recent lung function tests. Superoxide anion production by macrophages, studies of small airway integrity (closing volume, closing capacity, and the slope of Phase III of the single-breath nitrogen washout curve), and evaluation of alveolar gas exchange (diffusing capacity of carbon monoxide) were similar in both nonsmokers and marijuana smokers. However, tobacco smoking was associated with both significantly higher levels of superoxide anion release by pulmonary alveolar macrophages and significant abnormalities of small airway function and alveolar diffusing capacity. Based on the results of this study, pulmonary alveolar macrophages of marijuana-only smokers do not produce increased amounts of oxidants when compared to macrophages of non-smoking subjects. This observation may account for the absence of abnormalities in small airway function and alveolar diffusing capacity in marijuana-only smokers, in contrast to the presence of such findings in smokers of tobacco, regardless of marijuana use.

Adult↗

Respiratory symptoms and lung function in habitual heavy smokers of marijuana alone, smokers of marijuana and tobacco, smokers of tobacco alone, and nonsmokers.

To evaluate the possible pulmonary effects of habitual marijuana smoking with and without tobacco, we administered a detailed respiratory and drug use questionnaire and/or lung function tests to young, habitual, heavy smokers of marijuana alone (n = 144) or with tobacco (n = 135) and control subjects of similar age who smoked tobacco alone (n = 70) or were nonsmokers (n = 97). Mean amounts of marijuana and/or tobacco smoked were 49 to 57 joint-years marijuana (average daily number of joints times number of years smoked) and 16 to 22 pack-years of tobacco. Among the smokers of marijuana and/or tobacco, prevalence of chronic cough (18 to 24%), sputum production (20 to 26%), wheeze (25 to 37%) and greater than 1 prolonged acute bronchitic episode during the previous 3 yr (10 to 14%) was significantly higher than in the nonsmokers (p less than 0.05, chi square). No difference in prevalence of chronic cough, sputum production, or wheeze was noted between the marijuana and tobacco smokers, nor were there additive effects of marijuana and tobacco on symptom prevalence. We noted significant worsening effects of marijuana but not to tobacco on specific airway conductance and airway resistance (tests of mainly large airways function) in men and of tobacco but not of marijuana on carbon monoxide diffusing capacity and on closing volume, closing capacity, and the slope of Phase III of the single-breath nitrogen washout curve (tests reflecting mainly small airways function) (p less than 0.03, two-way ANCOVA). No adverse interactive effects of marijuana and tobacco on lung function were found.

Adult↗

Lung function of sheet metal workers exposed to fiber glass.

Out of 532 registered and contacted sheet metal workers, 251 responded, but only seven pairs were acceptable for the present study due to the following requirement: no history of smoking, pleural plaques or asbestos exposure. Seven of these workers were exposed daily to fiber glass, and seven were almost never exposed. In a second step nine additional exposed workers were included. Ordinary spirometry, lung volumes, closing volumes and the slope of the alveolar plateau, the maximum expiratory flow in air and after helium-oxygen breathing, and the elastic recoil pressures were measured. No evidence of small airway dysfunction or restrictive or obstructive ventilatory impairment was found, but the elastic recoil pressures of the exposed group were slightly increased. Fiber glass can conceivably cause a corresponding faint and probably harmless fibrous reaction in the lung parenchyma.

Adult↗

Airway function in sarcoidosis: smokers versus nonsmokers.

Pulmonary function was measured in 24 sarcoidosis patients, 17 nonsmokers and 7 smokers. 12 (4 smokers) had evidence of small airway disease and 6 patients (3 smokers) had evidence of large airway disease. A significantly greater proportion of smokers had an increased closing volume, and closing volume appears to be the most sensitive test for small airway disease in sarcoidosis. However, 3 patients with normal closing volumes had evidence of small airway disease by forced expiratory flow rates or frequency dependence of compliance. We conclude that there is a high incidence of small airway disease in patients with sarcoidosis. There also appears to be a synergism between sarcoidosis and smoking that leads to a significant degree of hyperinflation of the lung.

Adult↗

Influence of collateral ventilation on single-breath washout curves.

To examine the relationship between airway closure and collateral ventilation, Ar bolus single-breath washout tests were performed in the supine position in 10 mature dogs (animals with a well-developed collateral ventilation). Transpulmonary pressure was measured simultaneously to obtain the volume above residual volume of the inflection point in the pressure-volume curve (VIP). In pigs, closing volume (CV/VC%, mean 27.4%, where VC is vital capacity) equaled the volume of inflection (VIP/VC%, mean 35.1%) when the dead space (0.07 liter) was accounted for, indicating simultaneous onset. In dogs, closing volume (CV/VC%, mean 48.1%) was greater than the volume of inflection (VIP/VC%, mean 27%). Furthermore, as closing volume increased, so did the volume exhaled between closing volume and the volume of inflection [(CV-VIP)/VC%]. These increases were strongly age related, with the oldest dogs showing the greatest differences between closing volume and volume of inflection. These results support the previous suggestion that this difference is a measure of the degree of collateral ventilation. We defined a concavity index (CI) of phase IV by measuring the ratio of the end-to-mid phase IV height above extrapolated phase III (no concavity implies CI = 2). Whereas pigs had a low CI (mean 3.3), dogs had a high CI (mean 10.6). In dogs, the CI correlated well with closing volume (CV/VC%) and the volume exhaled between closing volume and volume of inflection [(CV-VIP)/VC%]. Again, this relationship was strongly dependent on age, suggesting that the CI is also a valid indication of the degree of collateral ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Airway closure during anesthesia: a comparison between resident-gas and argon-bolus techniques.

Airway closure was measured in awake and then anesthetized supine healthy subjects with the argon-bolus and the resident-gas (nitrogen) techniques simultaneously. The preinspiratory lung volume for the closing volume maneuver was varied from residual volume to closing capacity (CC). Comparative measurements were also performed in the upright and supine positions in awake subjects. Closing volume (CV) was consistently larger with the bolus technique in supine subjects both when awake and when anesthetized (difference between methods 0.1--0.2 l, P less than 0.01), whereas no difference between the methods was noted in upright subjects. The lower "nitrogen CV" in supine subjects may be due to a shorter vertical lung height with a smaller range of nitrogen concentrations, resulting in a less abrupt onset of phase IV (taken to indicate CV). CV was not significantly affected by the preinspiratory lung volume with either technique, and CC was unchanged when anesthesia was instituted. Functional residual capacity (FRC) was reduced with anesthesia (mean reduction: 0.6 l, P less than 0.01) and FRC-CC became negative in all subjects with either technique. This implies intermittent or continuous airway closure during anesthesia and the possibility of increased venous admixture.

Adult↗

Small airways response to naturalistic cat allergen exposure in subjects with asthma.

BACKGROUND: It is currently unclear whether the small airways (diameter <2 microm) contribute significantly to late asthmatic reactions to inhaled allergen. OBJECTIVES: We sought to determine whether naturalistic exposure to cat allergen induced late responses in the small airways as measured by pulmonary function testing and high-resolution computed tomography (HRCT) of the chest performed at end-expiration. METHODS: In a group of 10 subjects with cat-induced asthma, physiologic studies (spirometry and lung volumes, including closing volume) and HRCT were performed before and 6 and 23 hours after a cat room challenge that caused a 20% or greater acute fall in FEV(1). RESULTS: There was no significant decline in FEV(1) at 6 or 23 hours after cat exposure. Forced expiratory flow at 25% to 75% of forced vital capacity was significantly decreased at 6 hours after the challenge and returned to normal by 23 hours. HRCT image analysis as well as closing volume demonstrated increased air trapping from baseline at both 6 and 23 hours after the challenge. In addition, image analysis demonstrated a significant increase in small airways hyperresponsiveness to methacholine at 23 hours after the challenge. No significant mean changes were noted in lung volumes at either 6 or 23 hours or in PC(20) FEV(1) at 23 hours postchallenge. CONCLUSION: These findings demonstrate that naturalistic exposure to cat allergen results in significant small airways obstruction and hyperresponsiveness persisting for at least 23 hours, at which time these changes cannot be detected by conventional physiologic measures. CLINICAL IMPLICATIONS: Physiologically silent distal lung inflammation persists after an antigenic challenge.

Adult↗