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Several distinct cell adhesion molecule families have recently been identified and found to be important in the inflammatory response and for epithelial and endothelial homeostasis. The integrin family of adhesion molecules functions in both cell-matrix and cell-cell interactions, whereas the cadherins serve as important cell-cell receptors for maintenance of epithelial integrity. The leukocyte integrins, selectins, members of the immunoglobulin supergene family, and specific carbohydrates mediate adhesive interactions between leukocytes and endothelial cells. The mechanisms of leukocyte-epithelial adhesion are less well understood, but integrins and members of the immunoglobulin supergene family are also involved. The role of these molecules in pulmonary structure and inflammation is currently being actively explored. Further knowledge of these interactions, and the interplay of adhesion molecules, cytokines, and chemoattractants is likely to lead to novel therapeutic modalities in inflammatory diseases of the airway and lung parenchyma. In this overview, the families of adhesion molecules will be summarized, and their relevance for pulmonary structure and inflammation will be discussed.

To assess the manifestation and location of airway inflammation in smokers with chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD), we lavaged the airways of 12 smokers with CB and 11 smokers with COPD and coexisting CB (OCB). For comparison, the airways of 5 asymptomatic smokers (AS) and 10 healthy nonsmokers (HNS) were lavaged. In all cases, the first lavage aliquot, labeled "bronchial lavage" (BL), was processed separately from the four subsequent aliquots, which were combined and labeled "bronchoalveolar lavage" (BAL). The composition of BL and BAL fluids indicate an ongoing inflammatory process in the airways of all three groups of smokers. CB patients with obstruction had significantly lower concentrations of inflammatory cells in the BL and BAL fluids compared with subjects with nonobstructed CB. Furthermore, airway obstruction, indicated by a reduced FEV1, was significantly correlated with the concentrations of glutathione (p < 0.001), myeloperoxidase (MPO; p < 0.01), and eosinophil cationic protein (ECP; p < 0.01) in BAL fluids. Taken together, these findings suggest that the manifestations of inflammation present in the airways of smokers with CB are different in those who have developed obstruction compared with those who have not.

Sjögren's syndrome is characterized by a decrease in exocrine gland secretion and the destruction of secretory tissue and cells, that is, salivary and lacrimal glands. Although patients with Sjögren's syndrome have chronic cough and sometimes sputum, we have little knowledge concerning the morphology of their airways. We performed morphometric analysis of goblet cells and bronchial glands and compared them with intraluminal mucus volume by measuring the mucus-occupying ratio (MOR) in the airways of patients with Sjögren's syndrome. A total of 6 nonsmoking patients with Sjögren's syndrome who had no significant prolonged airway infections (Group SG) (6 women, 55 +/- 2 yr) were compared with four control patients with no pulmonary diseases (Group NL) (1 woman and 3 men, 64 +/- 2 yr) and five patients with chronic bronchitis (Group CB) (1 woman and 4 men, 52 +/- 5 yr). Autopsied lungs from 15 patients were used for morphometry by a digitalizing computer. Area proportion of bronchial glands (gland %) to bronchial wall, goblet cell-occupying ratio to total epithelial layer (goblet %), and MOR were measured in central (3-8 mm in diameter) and peripheral airways (2 mm or less in diameter). Gland % and goblet % in central and MOR in peripheral airways from Group SG were significantly larger than those from Group NL: 15 +/- 2 versus 6 +/- 1% (p < 0.01), 6 +/- 1 versus 2 +/- 1% (p < 0.05), and 9 +/- 2 versus 0.6 +/- 0.3% (p < 0.05), respectively. Further, these values from Group SG did not significantly differ from those from Group CB.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway inflammation is important in the development and progression of many pulmonary disorders, including asthma. We hypothesized that the hydrogen peroxide (H2O2) concentration in expired breath may be a marker of airway inflammation. Expired breath condensate was collected by cooling and the H2O2 concentration was measured fluorimetrically. Thirty-five samples were collected from 22 pediatric patients with asthma who were 7 to 18 yr of age and from 11 healthy, nonasthmatic controls. Asthmatic subjects were determined to be well or sick (acute disease of the upper or lower respiratory tract) by clinical examination. Pulmonary function tests were determined to be abnormal if there was a > 15% reduction in FEV1 or > 20% reduction in FEF25-75 compared with baseline values. Expired breath H2O2 was elevated in asthmatic subjects compared with controls (0.81 +/- 0.70 versus 0.25 +/- 0.27 mumol/L). The difference was primarily due to elevation of H2O2 in sick asthmatic subjects, whose expired breath H2O2 level of 1.5 +/- 0.5 (n = 10) was different from that of well asthmatics (0.54 +/- 0.56, n = 25). There was a high correlation between expired breath H2O2 and clinical status. Elevation of expired H2O2 occurred with either acute upper or lower respiratory tract disease. There was no statistically significant correlation between expired breath H2O2 level and pulmonary function test results. We conclude that elevation of H2O2 in the expired breath condensate is a simple, noninvasive method that can be used as a biochemical marker of airway inflammation.

The purpose of this study was to examine the effects of dexamethasone on airway responsiveness and lung inflammation of rats at 8 h, 32 h, and 7 d after allergen challenge. Brown-Norway male rats, 7 to 8 wk old, were actively sensitized to ovalbumin (OA) and challenged 14 d later. The rats were divided into a control group (n = 31) and a test group (n = 34) that received dexamethasone (DEXA) (0.3 mg/kg intraperitoneally) 14 h and 2 h before saline or OA challenge. For challenge, rats were anesthetized with pentobarbital and intubated endotracheally. Aerosols of OA (5% wt/vol in saline) were administered for 5 min. Responsiveness to inhaled aerosols of methacholine and the total and differential leukocyte counts in the large airways (generations 0 to 5), small airways, and parenchyma isolated by tissue mincing and digestion were measured at 8 h, 32 h, and 7 d after OA challenge. The cellular influx into the airways and parenchyma was highest at 8 h and decreased progressively over 7 d. DEXA significantly inhibited the cellular influx after allergen challenge. At 8 h, cellular return from the large airways was 3.61 +/- 0.5 x 10(6) (controls) versus 1.0 +/- 0.2 x 10(6) (DEXA), and from the small airways and parenchyma was 31.7 +/- 2.8 x 10(6) (controls) versus 21.9 +/- 2.9 x 10(6) (DEXA) (p < 0.05). The differences were attributable mostly to decreases in neutrophils in DEXA-treated animals. In control animals, neutrophil yield fell between 8 and 32 h, whereas eosinophils and 32 h, whereas eosinophil and lymphocyte counts increased.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA-DR and ICAM-I molecules play an important role in cellular interactions, and their expression can be induced by inflammatory stimuli. We evaluated the spontaneous expression of HLA-DR and ICAM-1 on epithelial cells obtained by bronchial brushing from 27 asthmatic patients, 10 chronic bronchitis (CB) patients, and 19 normal subjects. In all cases > 90% pure epithelial cells were obtained. HLA-DR and ICAM-1 were characterized using monoclonal antibodies and revealed by immunocytochemistry (APAAP technique). In asthma, the percentage of cells expressing HLA-DR and ICAM-1 was significantly increased by comparison with normal values (p < 0.001) and GB (p < 0.001; HLA-DR; p < 0.003; ICAM-1) and was correlated with the clinical score of Aas (p < 0.001, HLA-DR; p < 0.001, ICAM-1) and the FEV1 (p < 0.001, HLA-DR; p < 0.002; ICAM-1). In CB, expression of both markers was slightly but significantly increased by comparison with normal subjects and was correlated with FEV1 (p < 0.02, HLA-DR; p < 0.03, ICAM-1). In addition, the expression of HLA-DR and ICAM-1 was significantly correlated. This study suggests that epithelial cells are in an activated state in asthma and that the extent of expression of these markers may be specific to asthma, not a general feature of chronic inflammation.

To assess whether satisfying American Thoracic Society (ATS) end-of-test spirometry criteria can be enhanced by modifying the patient's expiratory technique, we conducted a cross-over trial of two expiratory techniques in 48 patients with a range of pulmonary functions (Group 1, n = 12: FEV1/FVC < 0.45; Group 2, n = 11: FEV1/FVC, 0.45 to 0.60; Group 3, n = 16: FEV1/FVC, 0.61 to 0.74; Group 4, n = 9: FEV1/FVC > or = 0.75). After randomizing the order of testing, each patient performed three exhalations using a "standard" forced expiratory maneuver and a modified expiratory technique consisting of an initial maximal expiratory effort followed by a "relaxed expiration" for as long as possible. Patients initiated "relaxed expiration" when instructed by the supervising technician, who issued the instruction to relax when expiratory airflow fell to < or = 200 ml/s (as determined by flow-volume loop analysis). ATS end-of-test criteria were satisfied significantly more often using the modified expiratory technique (58.3% of testing sessions) than using the standard technique (18.7% of sessions, p = 0.001) because of prolongation of the forced expiratory time (FET) with the modified technique in all patient groups. In the 38 patients with FEV1/FVC < or = 0.75, the largest FVC and FET rose significantly using the modified expiratory technique, without compromising the largest FEV1 in any group. In patients with FEV1/FVC > or = 0.75, FET increased without concomitant changes in FVC or FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)

The object of this study was to assess the relationship between occupational dust exposure and chronic obstructive pulmonary disease (COPD). Studies were identified using MEDLINE (January 1966 to July 1991), SCISEARCH, manual review of reference lists, and personal contact with more than 30 international experts. Studies of COPD, lung function, emphysema, chronic bronchitis, or mortality in workers exposed to nonorganic dust were retrieved. Studies were included if dust exposure was measured quantitatively, and a quantitative relationship between dust exposure and one of the outcomes of interest was calculated while controlling at least for smoking and age. Methodological rigor was assessed, and data regarding the study populations, prognostic factors, and outcomes were extracted independently by two reviewers. Thirteen reports derived from four cohorts of workers met our inclusion criteria. Three of the cohorts were of coal miners and one was of gold miners. All of the studies found a statistically significant association between loss of lung function and cumulative respirable dust exposure. It was estimated that 80 (95% CI, 34 to 137) of 1,000 nonsmoking coal miners with a cumulative respirable dust exposure of 122.5 gh/m3 (considered equivalent to 35 years of work with a mean respirable dust level of 2 mg/m3) could be expected to develop a clinically important (> 20%) loss of FEV1 attributable to dust. Among 1,000 smoking miners the comparable estimate was 66 (95% CI, 49 to 84). The risk of a clinically important loss of lung function attributable to dust among nonsmoking gold miners was estimated to be three times as large as for coal miners at less than one fifth of the cumulative respirable dust exposure (21.3 gh/m3), the maximal exposure observed among the cohort of gold miners. We conclude that occupational dust is an important cause of COPD, and the risk appears to be greater for gold miners than for coal miners. One possible explanation of the greater risk among gold miners is the higher silica content in gold mine dust.

Airway inflammation is increasingly recognized as a pivotal component of asthma. Because allergens provoke bronchial constriction and inflammation in allergic subjects, bronchial antigen challenge has emerged as a powerful technique for evaluating mechanisms involved in this process. In this study, we compare whole lung antigen challenge (WLAC) with segmental bronchoprovocation (SBP) in eight allergic, non-asthmatic, non-smoking subjects, and evaluated the response by bronchoalveolar lavage (BAL) prior to, and 48 h after antigen challenge. Both challenge techniques evoked airway inflammation, manifest as an increase in total cells and eosinophils recovered by BAL, an increase in total protein concentration, and enhanced production of superoxide anion by airspace cells. The degree to which these changes occurred was significantly greater with SBP than WLAC, and only SBP evoked persistent measurable change in alveolar macrophage density and eosinophil granule protein concentrations. Moreover, although both techniques were associated with a comparable immediate fall in FEV1, only WLAC resulted in statistically significant persistent physiologic changes 48 h afterwards. We conclude that, as anticipated, SBP produces more intense airway inflammation in allergic subjects, does not result in late airway obstruction, and offers specific advantages in studying allergen-driven airway inflammation.

Chronic bronchitis is associated with airways obstruction and inflammation. In order to determine whether aerosolized beclomethasone can modulate airway inflammation and diminish airway obstruction, subjects with chronic bronchitis performed spirometry and underwent bronchoalveolar lavage (BAL) before and after receiving 6 wk of therapy (five puffs four times a day) with either aerosolized beclomethasone (n = 20) or placebo (n = 10) in a double-blinded, randomized fashion. All subjects received aerosolized albuterol before each use of the study medications. Before BAL, the airways were visually assessed for the appearance of inflammation and assigned a score, the bronchitis index. BAL was performed by instilling five 20-ml aliquots of saline into each of three sites and pooling and separately analyzing the returns from the first aliquots to yield a "bronchial sample." The bronchial lavages were repeated in an additional three sites to increase the volume of fluid available for analysis. The fluid was prepared for cytologic examination by cytocentrifugation. Albumin (as a measure of epithelium permeability) and lactoferrin and lysozyme (as measures of serous cell activity) were measured in unconcentrated BAL fluid by enzyme-linked immunosorbent assay, and concentrations in epithelial lining fluid were estimated using urea as an internal marker for dilution. After treatment, the beclomethasone group, but not the placebo group, showed improvement in FVC (p = 0.02), FEV1 (p = 0.002), and 25 to 75% forced expiratory flow (p = 0.006). Associated with the improvement in spirometry, the bronchitis index fell (13.5 +/- 1.0 versus 10.75 +/- 1.1, p = 0.02) in the beclomethasone-treated group, but not the placebo-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Excessive production of sputum is one of the major symptoms in patients with chronic airway diseases. Because endogenous prostaglandins may play a role in the regulation of airway secretions, blockade of cyclooxygenase pathway with indomethacin could decrease respiratory tract fluid and mucus by inhibiting Cl secretion and glandular secretion and by enhancing Na absorption across airway mucosa. To test this hypothesis, we studied the effect of inhaled indomethacin on bronchorrhea in patients with chronic bronchitis, diffuse panbronchiolitis, and bronchiectasis in a double-blind, placebo-controlled fashion. Patients who inhaled 2 ml of indomethacin (1.2 micrograms/ml) three times a day for 14 days showed a decrease in the amount of sputum, from 189 +/- 19 to 95 +/- 21 g/day (p less than 0.001) and an increase in the solid component of sputum without alterations in parameters of systemic inflammatory responses. Although pulmonary function remained unchanged, perceived dyspnea was improved so that Borg's ratio scale was decreased from 7.1 +/- 0.5 to 4.5 +/- 0.4 (p less than 0.01). Adverse effects, including hypotension and bronchoconstriction, were not observed. The reduction of sputum was accompanied by a significant decrease in the concentrations of prostaglandin (PG)E2, PGF2 alpha, thromboxane B2, and 6-oxo-PGF1 alpha in the sputum. Thus, indomethacin inhalation may be of value in reducing bronchorrhea sputum, probably through the inhibition of PG-dependent airway secretions.

To evaluate the effectiveness of the current workplace standards in preventing chronic health effects from cotton dust exposure, a 5-yr longitudinal study of a large multimill population of cotton textile and synthetic process workers, employed at a major U.S. textile company, was conducted. To control for and assess the effect of type of work area on annual change in lung function, we limited the analysis to those 1,817 subjects who, throughout their textile work history at the company, worked exclusively in cotton yarn manufacturing or slashing and weaving, or in synthetic textile mills. The expected effect of smoking on average annual change in lung function was demonstrated for both cotton and synthetic workers. Despite lower overall dust exposure, cotton yarn workers exhibited steeper annual declines in lung function than did workers in slashing and weaving; this difference persisted within each smoking category, indicating a dust potency effect. There were mill differences in annual change in lung function among cotton workers, potentially masking an exposure effect. A smoking-work area interaction persisted after adjusting for mill differences, with the largest annual declines observed in cotton yarn workers who smoke. A significant dose-response relationship was seen in cotton yarn manufacturing between annual declines in FEV1, FVC, and FEF25-75 and average exposure by mill, and the larger declines were found in mills using the highest percentage and lowest grade of cotton. Synthetic textile workers had larger declines than did cotton textile workers, which were not explained by smoking or duration of employment. Unrecognized and unmeasured causative exposures or selection bias could explain this result.(ABSTRACT TRUNCATED AT 250 WORDS)

This study reports on the relationship of airway hyperresponsiveness (AH) with respiratory symptoms and diurnal peak flow expiratory (PEF) variation in 221 hyperresponsive patients with moderately severe airways obstruction. The disease was in a stable phase in all patients. Closely adhering to the American Thoracic Society criteria, patients were divided into three syndrome diagnoses based on a standardized history: asthma (n = 81), asthmatic bronchitis (AB, n = 69), and chronic obstructive pulmonary disease [( COPD] n = 44); 27 subjects could not be placed in any group. Mean (+/- SEM) log2 PC20 histamine values were significantly lower in the asthmatic group (-2.77 +/- 0.20 mg/ml) than in the COPD (-0.89 +/- 0.29 mg/ml) and AB groups (-1.37 +/- 0.25 mg/ml; one-way ANOVA, p less than 0.001). However, considerable overlap of individual responses existed. Differences between the groups could not be attributed to differences in prechallenge FEV1 levels. For every level of FEV1, asthmatic subjects were more hyperresponsive than patients with COPD. The dependence of PC20 on prechallenge FEV1 was comparable in all groups. There was a significant correlation between the degree of AH and diurnal PEF variation (rho = -0.401, p less than 0.001), which was stronger in asthma (rho = -0.409) than in COPD (rho = -0.325). Despite this obvious association, a wide range of diurnal PEF variation values existed for every level of PC20, indicating that PEF variability and AH are not interchangeable. The relationships between symptoms and both AH levels and PEF variation were weak. No significant differences were found between syndrome diagnosis groups with respect to diurnal PEF variation.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison was made of total respiratory resistance (Rrs) and reactance (Xrs) determined between 6 and 26 Hz by means of a forced oscillation technique in 27 patients with asthma (group A), 28 patients with chronic bronchitis (group B), and 20 patients with emphysema (group E) to examine whether the method can provide data capable of distinguishing among these diseases. The three groups demonstrated a similar reduction in the FEV1. In addition, static and dynamic lung volumes, maximal expiratory flows, diffusing capacity for CO, airway resistance (Raw), and elastic lung recoil were measured. The observed alterations of Rrs and Xrs consisted of an increase in Rrs, a decrease in Rrs with frequency, and a decrease in Xrs. However, significant differences were found between the three groups: Rrs at 6 Hz and average Rrs were most increased in group A, whereas the negative frequency dependence of Rrs and the decrease in Xrs were least pronounced in group E. In all groups Rrs at 6 Hz, the average slope of Rrs, and the average level of Xrs were tightly interrelated and showed in addition a high correlation with airway resistance; the correlations with FEV1 were less satisfactory. Discriminant analysis performed on the complete set of data, excluding diffusing capacity and elastic lung recoil, which were used as selection criteria, demonstrated that forced oscillation parameters were the most important factors discriminating among the groups.

In a cross-sectional study of a working population of black South African gold miners, 1,197 men were studied with respiratory and occupational questionnaires, lung function tests, and chest radiographs. The study was designed to examine the effects of silicosis on respiratory symptoms and lung function. A total of 857 men with chronic, simple silicosis and 340 men without silicosis were included in the sample. Other determinants of lung disease including the duration and intensity of underground dust exposure and tobacco smoking were also examined. Three distinct pulmonary disorders could be discerned: silicosis-associated pulmonary dysfunction with dyspnea on effort; chronic airflow limitation, which was related to the duration of underground exposure; and a chronic bronchitic symptom complex, which reflected the intensity of dust exposure in the workplace. Chronic, uncomplicated silicosis was found to be associated with significant loss of lung function, and all of the measured indices, FVC, FEV1, FEV1/FVC%, maximal midexpiratory flow rate (MMEF), and lung diffusion for carbon monoxide measured by the single-breath method (DLCO) were reduced. When comparing men with Category 3/3 nodule profusion with men without silicosis, reductions of FVC of 351 ml, FEV1 of 447 ml, MMEF of 1.04 L/s, and DLCO of 4.7 ml/min/mm Hg (p = 0.0001) were detected after controlling for age, height, the direct effects of the underground environment, and tobacco smoking. Dyspnea on effort was more common in the men with silicosis (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Cystic fibrosis (CF) is characterized by excessive amounts of thick and tenacious mucous secretions that obstruct organ ducts and passages. In the respiratory tract this is associated with chronic infection resulting in the hypersecretion of purulent sputum, which the patient finds difficult to clear. We have studied the rheologic properties of purulent sputum from six patients with CF and five patients with chronic bronchitis to assess whether CF is associated with increased sputum viscoelasticity. In addition, we have isolated the major rheologic determinants, mucous glycoproteins, from CF and chronic bronchitis sputa and, using a magnetic microrheometer, investigated the possibility that the altered properties of mucus in CF are associated with abnormalities in these glycoproteins. Creep compliance analysis indicated that the CF sputa possessed raised levels of both elasticity (p less than 0.01) and viscosity (p less than 0.01). These increases in both rheologic parameters were found to be associated with increases in the DNA content (p less than 0.01) and dry weight (p less than 0.05). Mucous glycoproteins were isolated from CF and chronic bronchitis sputum samples by gel filtration on Sepharose CL4B, followed by concentration to form 8% wt/wt gels. In the absence of other sputum components, no abnormality in the rheologic properties of CF mucin gels could be detected. However, when DNA was added, the CF gels responded with increases in both elasticity and viscosity of as much as 30% (p less than 0.05), an effect not observed in the chronic bronchitis gels. These results suggest that a subtle abnormality may exist in CF mucous glycoproteins and that this could have a role in the altered physical properties of mucous secretions in CF.

Studies in humans suggests that airway inflammation may modulate nonspecific airway responsiveness. We studied in a rat model the effect of the inhalation of endotoxin on the cellular composition of the bronchoalveolar lavage (BAL) fluid and airway responsiveness. The exposure to an aerosol of endotoxin caused a rapid influx of neutrophils in the airways. The neutrophils persisted up to 24 h after exposure. Elastase activity in lavage fluid became detectable 30 min after the endotoxin exposure and peaked 9 h later. The exposure to the endotoxin aerosol was followed 1 to 2 h later by a significant increase in the airway responsiveness to 5-hydroxytryptamine (5HT). However, the increase in responsiveness disappeared, and 9 to 12 h following the end of the exposure a significant decrease in airway 5HT responsiveness was observed at the moment that more than 80% of the cells contained in the BAL fluid were neutrophils. The effect of endotoxin on airway responsiveness and inflammation was dose dependent. We also compared in three different inbred rat strains the effect of endotoxin inhalation. The aerosol exposure induced in all three strains a comparable neutrophil influx in the airways, but only two of the three strains became hyperresponsive to 5HT. We conclude that the inhalation of endotoxin causes a neutrophilic airway inflammation in rats. The relationship between this airway inflammation and airway responsiveness is dependent on the time following the exposure and the animal strain used.

Patients with chronic obstructive bronchitis commonly suffer acute, transient exacerbations, which suggests that episodic bronchoconstriction may play a role in this disease. We studied 22 patients with chronic obstructive bronchitis and no acute improvement in pulmonary function after inhaled sympathomimetics, using methacholine bronchial provocation tests to evaluate the incidence of bronchial hyperreactivity. Patients with clinical or laboratory findings indicative of asthma were excluded. The group demonstrated significant baseline airway obstruction (mean +/- SD forced expiratory volume in one second, 0.96 +/- 0.44) and no improvement after inhalation of isoproterenol (1.68 +/- 8.54% baseline change). All patients were very sensitive to inhaled methacholine, reacting at a dose of 4.29 +/- 5.49 cumulative units. There were no normal responses. These data suggest that airway hyperreactivity may contribute to acute, transient exacerbations experienced by patients with chronic obstructive bronchitis, even in the absence of acute improvement in pulmonary function after the administration of sympathomimetics, and may warrant chronic prophylactic bronchodilator therapy.

A unique data set of 3,380 British coal miners has been reanalyzed with major focus on nonpneumoconiotic respiratory conditions. The aim was to assess the independent contribution of smoking and exposure to respirable dust to clinically significant measures of respiratory dysfunction. Exposure to coal-mine dust was monitored over a 10-yr period. Medical surveys provided estimates of prior dust exposure and recorded respiratory symptoms. Each man's FEV1 was compared with the level predicted for his age and height by an internally derived prediction equation for FEV1. Four respiratory indices were considered at the end of the 10-yr period: FEV1 less than 80%, chronic bronchitis, chronic bronchitis with FEV1 less than 80%, and FEV1 less than 65%. Results were uniformly incorporated into logistic regression equations for each condition. The equations include coefficients for age, dust, and when indicated, an interaction term for age and dust. Dust-related increases in prevalence of each of the 4 conditions were statistically significant and were similar for smokers and nonsmokers at the mean age (47 yr). There was no evidence that smoking potentiates the effect of exposure to dust. Estimates of prevalences at the mean age of all 4 measures of respiratory dysfunction were greater in smokers. At intermediate and high dust exposure the prevalence of the 4 conditions in nonsmokers approached the prevalence in smokers at hypothetically zero dust exposure. Both smoking and dust exposure can cause clinically important respiratory dysfunction and their separate contributions to obstructive airway disease in coal miners appear to be additive.(ABSTRACT TRUNCATED AT 250 WORDS)

It was not possible to demonstrate an increase in the proportion of goblet cells in the bronchioles of patients with chronic bronchitis and no emphysema, whereas other lesions, such as mucous gland hyperplasia, airway narrowing, and airway mucus were easily demonstrated in similar cases. Thus, it seems that goblet cell metaplasia is not an important factor in patients who have chronic bronchitis but little evidence of chronic airflow obstruction. Goblet cell metaplasia is an obvious feature of patients with chronic bronchitis and emphysema, especially in those with symptomatic or fatal chronic airflow obstruction, and it may be responsible for producing obstruction in the peripheral airways of these subjects. The role of goblet cell metaplasia in smokers with little airflow obstruction is uncertain from the data presented. No difference was noted in the proportion of goblet cells between bronchitic patients and nonbronchitic smokers who did not have clinical airflow obstruction.

To investigate the role of leukocytes and neutrophils in the peripheral blood on airway responsiveness, we studied nine patients with chronic bronchitis and histologically proved bronchial carcinoma before and after chemotherapy. The concentration of methacholine (in mg/ml) necessary to increase specific airway resistance by 100%, PC100SRaw, and the number of leukocytes and neutrophils (in cells x 10(6)/ml) were measured before, and 8 and 16 days after chemotherapy. Mean (SEM) total number of leukocytes decreased significantly (p less than 0.001) from 9.0 (0.8) to 4.4 (0.6) and 3.4 (0.4), and mean (SEM) number of neutrophils decreased significantly (p less than 0.005) from 5.1 (0.7) to 2.8 (0.5) and 1.0 (0.4), respectively. Mean (SEM) PC100SRaw was 3.3 (0.9) at baseline and 3.5 (1.2) and 3.8 (1.0) mg/ml at Days 8 and 16, respectively, without significant differences. These data suggest that a significant chemotherapy-induced leukocyte depletion in the peripheral blood does not influence airway responsiveness in patients with chronic bronchitis and bronchial carcinoma.

Almitrine bismesylate is a new, orally administered, respiratory stimulant that improves arterial blood gas tensions in patients with chronic bronchitis and emphysema, and it may have an effect on the pulmonary circulation and on right ventricular performance. We have, therefore, compared the effects of Almitrine with those of oxygen (given as 3 L/min by nasal prongs) on arterial blood gas tensions, mean pulmonary arterial pressure (Ppa), and right ventricular ejection fraction (RVEF) measured both at rest and during exercise in patients with chronic hypoxemia caused by chronic bronchitis and emphysema. Arterial oxygen tension improved significantly both at rest and during exercise after either 100 mg Almitrine by mouth or when breathing oxygen, both at rest and during exercise. Almitrine increased the mean Ppa at rest from 22 +/- 4 to 35 +/- 5 mmHg (p less than 0.001), and mean Ppa rose further during exercise from 38 +/- 5 mmHg before Almitrine to 49 +/- 7 mmHg (p less than 0.001) after Almitrine. In contrast, oxygen breathing did not change Ppa when at rest but reduced the amount of rise in Ppa during exercise. The change in Ppa after Almitrine correlated with the plasma Almitrine concentration (r = 0.69, p less than 0.05) and was associated with a fall in RVEF at rest from 0.38 +/- 0.03 to 0.32 +/- 0.02 (p less than 0.001). In 5 of the patients who received 50 mg of Almitrine by mouth twice daily for 3 months, the Ppa both at rest and during exercise remained significantly higher than in the control study before receiving Almitrine, but RVEF was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied central and peripheral airways as determinants of ventilatory function in patients with chronic bronchitis (CB), bronchial asthma (BA), and emphysema (CPE), which were identified using the selective alveolobronchogram (SAB) (see reference 14). First, the relationship between SAB and morphologic findings in the airway was examined in 16 autopsy lungs. The irregularity indices of both central (C-II) and peripheral airways (P-II), obtained from SAB, showed a significant correlation with pathologic abnormalities in both airways (p less than 0.01). Second, SAB were obtained in 38 CB, 25 BA, and 62 CPE patients in whom pulmonary function tests were performed. In CB, C-II were significantly correlated with P-II (p less than 0.001). In CB, inspiratory lung resistance (RL) was significantly correlated with P-II (p less than 0.001) and with C-II (p less than 0.01), and FEV/VC% was significantly correlated with P-II (p less than 0.0001) but not with C-II. In BA and CPE, little correlation was observed between any SAB parameter and RL or FEV/VC%. We conclude that the present SAB parameters represent morphometric abnormalities of the central and peripheral airways, and that in CB, peripheral airway abnormalities correlated well with chronic airway obstruction.

A resurgence of interest in clinical auscultation is in progress. Recent technical advances permit more objective observations than were previously possible. Quantified lung sounds are being correlated with clinical, physiologic, and roentgenologic information. The purpose of this article is to summarize current knowledge on the production, transmission, and clinical significance of lung sounds. The complex sonic signals arising in the lung during respiration reflect its mechanical state. More precise understanding of pulmonary sounds and their clinical correlations could lead to powerful diagnostic tools, which have particular appeal because of their noninvasive nature.

Hemodynamic values obtained during right heart catheterization in about 35 patients with chronic bronchitis were compared with the same variables 3.3 years later (range, 2 to 5 years). In the group of 13 patients with mean pulmonary arterial pressure less than 20 mm Hg at the first catheterization, the average value was 15.8 mm Hg at rest and 25.2 mm Hg during moderate exercise at the first investigation, and 16.9 and 26.3 mm Hg, respectively at the second catherization; the changes were not significant. In the group of pulmonary hypertensive patients, the mean pulmonary arterial pressure was 27.0 mm Hg at rest and 44.1 mm Hg during moderate exercise at the first catheterization, and 26.8 and 38.9 mm Hg, respectively, at the second catheterization. Thus, even in this group, there was no deterioration in pulmonary hemodynamics, because there was no significant change in right or left filling pressure, or in cardiac output. There was, however, a marked decrease in systemic arterial pressure, which was significant in the group with pulmonary hypertension. This decrease in left ventricular afterload could be partly responsible for the stabilization of pulmonary hemodynamics, and it could be due to the peripheral vasodilating effect of hypoxia and hypercapnia.

We studied the relation between selective alveolo-bronchograms (SAB) and pulmonary function tests in patients with chronic obstructive pulmonary disease (COPD) other than asthma. The SAB were obtained by the technique reported by Nakamura and coworkers (Tohoku J Exp Med 1969; 99:207). First, the relation between SAB and morphologic findings was examined in 14 autopsy lungs in order to confirm the morphologic bases of the shadows. The ring shadows that appeared in the SAB were histologically identified as alveolar ducts in normal lungs and as destroyed parenchymal air spaces in emphysematous lungs. There was a significant correlation between the mean diameter of ring shadow (DR) and the degree of morphologic emphysema (p less than 0.001). This correlation indicated a significant degree of emphysema when the DR exceeded 900 micron. The irregularity index of the airway in SAB also showed a significant correlation to the grade of pathologic abnormalities in the airways (p less than 0.01). Second, SAB were obtained in 64 patients with COPD in whom pulmonary function tests were performed. In these patients, the DR correlated significantly with most of the pulmonary function tests. This correlation was especially high with transfer factor (DLCO/VA). These 64 patients were divided into 2 groups on the basis of the DR: In Group A, DR was more than 900 micron, whereas in Group B, it was less than 900 micron. In Group A, the DR also showed a significant correlation with DLCO/VA and with diffusing capacity (DLCO); in Group B, significant correlations were found in the irregularity index, especially with regard to pulmonary resistance and the ratio of forced expiratory volume in one second to vital capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Six male subjects with chronic bronchitis were given a single aerosol dose of atropine sulfate (0.05 mg/kg). Spirometry and venous blood samples were obtained before and at 0.25, 0.5, 1.0, 1.5, 2.0, and 4.0 h after inhalation of drug. All subjects had a satisfactory bronchodilator response and detectable serum concentrations of atropine within 15 min. Measurable serum concentrations persisted for 4 h with apparent continued slow absorption occurring throughout the entire time interval. The maximal concentrations achieved ranged from 1.3 to 5.8 ng/ml in five subjects. A sixth subject achieved much higher concentrations (as high as 21 ng/ml) and experienced systemic side effects. This latter concentration is comparable to those achieved with doses of 1.5 to 2.0 mg of parenteral atropine. Significant systemic absorption may occur after inhalation of atropine sulfate, although the degree of absorption is variable.

Bronchial injury was induced in 7 dogs by exposure to nebulized 1% nitric acid 3 days per week for 4 weeks. Lung mechanics were measured prior to exposure, at the completion of exposure, and at 1, 3, and 5 months postexposure. Airway obstruction persisted unabated throughout the postexposure period, with significant reductions in maximal expiratory flows. Pulmonary resistance, the slope of phase III, and the volume of isoflow were increased. Hyperresponsiveness to histamine developed between 3 and 5 months. Histologically, there was minimal damage to the cartilaginous airways. Widespread chronic inflammation with minimal fibrosis was seen in the membranous bronchi and respiratory bronchioles. Pathology scores for cartilaginous and noncartilaginous (small) airways were developed and correlated with tests of airway function. Small airways pathology scores correlated with flows at 50 and 25% of the vital capacity and with pulmonary resistance. Density dependence of maximal expiratory flow, closing volume, and closing capacity failed to correlate with either the airway obstruction or the small airways pathology scores.

The anticholinergic, antimuscarinic compounds are potent and hitherto neglected bronchodilators. Although atropine itself has drawbacks, principally related to its rapid absorption and consequent systemic side effects, its quaternary ammonium congeners, atropine methonitrate and ipratropium bromide, are poorly absorbed. When given by inhalation, they are as effective bronchodilators as atropine is, but longer acting and much less prone to side effects. They act predominantly at a site that is different from adrenergic agents and thus afford an alternative, complementary approach to the treatment of airways obstruction. In stable asthmatic subjects, ipratropium is almost as potent a bronchodilator as beta 2-adrenergic agents are. In patients with chronic bronchitis and emphysema, it is more potent than beta 2-adrenergic agents are. In both conditions, its combination with other bronchodilators adds significantly to the level and duration of bronchodilatation. It may also be occasionally useful in counteracting bronchospasm caused by specific stimuli, such as cold air and exercise, and particularly that caused by inadvertent beta-adrenergic blockade. By inhalation, ipratropium is relatively free of side effects, even in doses as much as 20 times those that produce maximal bronchodilatation. It does not significantly affect mucus production, viscosity, or clearance, problems for which atropine is suspect. Nor does it produce tremor and tachycardia, as do adrenergic agents. It can also probably be safely used in patients with glaucoma and bladder neck obstruction, unlike atropine. Ipratropium will probably find its major application in the long-term management of chronic bronchitis and emphysema, and in asthmatic patients who are poorly controlled by, or who experience troublesome side effects from, adrenergic agents.

Persons from 148 randomly selected households in an urban community were screened in their homes using a modified British Medical Research Council respiratory disease questionnaire and a portable spirometer. Analysis showed a significant tendency for chronic bronchitis to aggregate within households. Significant aggregation was observed for 1-sec forced expiratory volume, when measured as the per cent of the predicted value or as a score calculated from the data. The 1-sec forced expiratory volume was significantly correlated between siblings, but less clearly so between spouses. Correlation of 1-sec forced expiratory volume between mother and child appeared to be confounded by maternal smoking habits, an effect most notable between mothers and male offspring. The 1-sec forced expiratory volume of fathers was significantly correlated with that of their children, especially female children, an effect that appeared to be independent of smoking habits.

Chronic bronchitis was induced in 7 dogs of mixed breed by chronic exposure to SO2 gas. Within the first 2 to 4 wk of exposure, the dogs developed cough and mucous hypersecretion, chronic airway obstruction (increased pulmonary resistance), and persistent lung inflammation as demonstrated by an increase in the number of neutrophils recovered in the bronchoalveolar lavage (BAL) fluid. Airway responsiveness to methacholine aerosol decreased 2- to 3-fold within 8 wk of SO2 exposure. In contrast, airway responsiveness to intravenous administration of methacholine did not change. The data suggest that the decreased airway responsiveness observed during persistent pulmonary inflammation in SO2-exposed dogs is not due to an altered state of airway contractile elements but likely reflects expression of an inhibitory influence of the mucoepithelial barrier.

Maximal mid-expiratory flow (MMEF), maximal expiratory flow volume (MEFV) curves obtained with a wedge spirometer, and nitrogen closing volumes were determined in 38 patients with mild airway obstruction. Seventeen patients had asthma in remission and 21 had bronchitis. In all of them the forced expiratory volume in one second was within the normal range. Results were compared with predicted data in the literature and with a group of normal control subjects. In the patients with asthma, compared to predicted flow rates, MMEF was abnormal in 5, MEFV curves were abnormal in at least 8; closing volume was abnormally increased in only one patient, and an abnormal slope of the alveolar plateau was present in 4 additional patients. In the patients with bronchitis, compared to predicted flow rates, -MEF was reduced in 5, MEFV curves were abnormal in at least 7; increased closing volumes were present in 6, and the slope of the alveolar plateau was abnormal in 3 other patients. When flow rates were compared with those of normal control subjects, MMEF was about as frequently abnormal as MEFV curves, suggesting that the discrepancy between abnormal MMEF AND MEFV curves was due to variability of the predicted data. The results indicated that flow rates can be abnormal in subjects with normal closing volumes and a normal slope of the alveolar plateau, and that MEFV curves can be more sensitive than closing volume in detecting abnormalities in patients with mild airway obstruction. The results suggested that the use of both MEFV curves and the closing volume test for screening would defect functional abnormalities more frequently than either test alone.

The radioaerosol method was used to measure the effect of saline aerosol on the rate of clearance of secretions from the lung. Two trial runs were done in each of 7 patients with chronic obstructive lung disease (mean +/- SD ratio of 1-sec forced expiratory volume for forced vital capacity, 50 +/- 15 per cent), a control run and a saline run. In both runs, 5.0 +/- 0.7-micron polystyrene particles tagged with 99mTc were inhaled under controlled conditions by the patients, and their subsequent clearance was monitored for 6 hours by whole lung counters. Scanning was also done with a gamma rectilinear scanner. The saline run was identical to the control run except that 30 min after inhaling the radioaerosol the patient inhaled an aerosol of hypertonic (1.21 M) saline for 11 min from an ultrasonic nebulizer. Although the initial distribution of the radioaerosol along the airways was the same in both runs, whole lung clearance during the first 50 min was twice as fast after the inhalation oft he hypertonic saline aerosol as in the control (P less than 0.01). The mean weight of sputum produced was higher (P less than 0.05) in the saline run. The number of coughs in the 2 runs was the same.

We have assessed bronchial mucous gland size in a group of 26 patients with severe chronic air-flow obstruction and hypoxemia from the NIH Nocturnal Oxygen Therapy Trial. These patients had their sputum volume assessed at least 4 times when free from exacerbations. Mucous gland size was assessed by the gland/wall ratio (Reid Index), by absolute gland area, and by the volume proportion of glands. The volume of sputum produced was significantly related to the volume proportion of mucous glands (Rho = 0.53, p less than 0.01) and to the absolute gland area (Rho = 0.49, p less than 0.05), but not to the Reid Index, (Rho = 0.35, p greater than 0.05). Volume proportion of glands can be easily and quickly measured using a computer-assisted digitizer, and it is the method of choice for measuring mucous gland size in this series. Neither the Reid Index nor the volume proportion of glands was related to the forced expiratory volume in one second (FEV1), and the measurements were not significantly related to each other. The amount of sputum produced was not related significantly to the FEV1 (Rho = 0.26, p greater than 0.05).

Characteristics of subjects with nonreproducible lung function tests (test failures) are described in two studies of occupational respiratory disease. According to current guidelines for spirometry, subjects with test failure are excluded from analyses of epidemiologic pulmonary function data. Among 415 Chinese cotton textile workers, the prevalence of byssinosis was 5.8% for subjects with repeatable tests and 13.3% for subjects with test failure. In regression analysis, the estimate of the association between cotton dust exposure and FEV1 decreased when subjects with test failure were excluded. In a second cohort of 378 asbestos-exposed machinists, the prevalence of chronic bronchitis was significantly greater among those with test failure. Considering only subjects with repeatable measurements, FEV1 was lower among textile workers with byssinosis and machinists with chronic bronchitis than among their asymptomatic coworkers. This suggests that, on average, subjects with poor test performance had lower (unobserved) FEV1 values, and therefore that the exclusion of subjects with test failure may cause selection bias.

Chronic bronchitis was induced in 6 mongrel dogs by chronic exposure to SO2 gas; the degree of chronic airway obstruction and the effects on airway responsiveness to inhaled histamine, carbachol, and prostaglandin F2 alpha were examined. Five dogs developed chronic airway obstruction, as indicated by an increase in pulmonary resistance, and clinical mucous hypersecretion. In addition, in each of the animals in which chronic airway obstruction developed there was a decrease in the airway responsiveness to inhaled mediators. Those findings demonstrate that induction of chronic bronchitis in dogs results in hyporesponsiveness to inhaled mediators, a finding distinctly different from that reported in human subjects with naturally occurring disease.

Chronic bronchitis was induced in 6 mongrel dogs by exposure to SO2 gas for 6 to 18 months. All of the dogs developed cough and mucus hypersecretion. Chronic airway obstruction and decreased airway responsiveness to inhaled histamine developed in 5 of the dogs. Histologic changes in dogs evaluated after SO2 exposure included significant mucous gland hypertrophy and hyperplasia, epithelial thickening, and a decrease in the number of luminal cells containing undischarged secretory granules. Acute and chronic inflammation were found in the dogs with airway obstruction and decreased responsiveness to histamine, but such inflammation was absent in the one dog that failed to develop physiologic changes. After a period of recovery from SO2 exposure of 9 to 21 months, inflammation regressed dramatically and the other histologic changes returned toward normal. Physiologic changes regressed somewhat in those dogs that had had changes. These findings suggest that inflammation may be an important factor influencing the development of airway obstruction and altered airway responsiveness in the setting of chronic bronchitis.

To determine the relationship between gastroesophageal (GE) reflux and pulmonary disease, we studied 21 asthmatics, 30 chronic bronchitics, 6 patients with GE reflux and no pulmonary symptoms, and 10 control subjects; GE reflux was diagnosed by pH monitoring and GE scintiscanning. Frequency of GE reflux in the asthmatics was 57%; in the chronic bronchitics it was 56%. Pulmonary function tests did not show any differences between patients with or without reflux. The GE reflux episodes were more numerous but shorter in asthmatics than in chronic bronchitics. Patients with digestive symptoms alone were no different from chronic bronchitics with respect to reflux. The mechanism whereby reflux triggers pulmonary problems was investigated using the following 2 tests: scintiscan for pulmonary aspiration, and esophageal acid infusion (0.1N HCl). Six pulmonary aspirations were detected. Only asthmatics, with or without reflux, showed any significant variations in maximal expiratory flow at 50% and 25% of VC after HCl infusion. Thus, our results show that asthmatics differ from chronic bronchitics by the characteristics of their reflux.

Seven adult mongrel dogs were exposed to SO2 gas at 2 different concentrations (15 and 50 ppm) on a daily basis for 5 to 11 months. Mucous hypersecretion and airway obstruction (a sustained increase in pulmonary resistance) developed in 4 dogs exposed to 50 ppm SO2. Histologic examination of the dogs' airways demonstrated epithelial thickening and an increase in size of the mucous glands. No inflammatory cell infiltration of the airways was noted and, in addition, responsiveness to inhaled histamine and methacholine did not change. The increase in lung resistance correlated with increase in mucous gland volume and airway wall thickening, but not with any change in airway responsiveness. Dogs exposed to 15 ppm SO2 showed minimal histologic and physiologic changes compared with control dogs. Previous work with a similar model of chronic bronchitis, using higher level SO2 exposure, has demonstrated an association of airway inflammation with decreased responsiveness to inhaled bronchoconstrictors. In the present study, with a lower exposure level to SO2 (50 versus 200 ppm), we found similar histologic findings associated with airway obstruction, but in the absence of airway inflammation, responsiveness to inhaled bronchoconstrictors was unchanged. This supports the theory that chronic airway inflammation may be associated with decreased responsiveness to inhaled bronchoconstrictors. This contrasts with the hyperresponsiveness induced by acute exposure to irritant gases noted by others.

To test the hypothesis that acute inflammation in peripheral airways can cause changes in airway function, we measured lung mechanics and assessed postmortem histology in 20 dogs. After baseline measurements of subdivisions of lung volume, pressure volume curves, pulmonary resistance (RL), dynamic compliance (Cdyn), closing capacity (CC), and the slope of phase 3 of the single breath N2 washout curve (delta N2/L), 10 dogs breathed nebulized 0.25% HCl (Group 2) and 10 breathed nebulized normal saline (Group 1). Measurements were repeated at 90-min intervals for 4 h. Animals were killed and 1 lung fixed in inflation and sampled for quantitative histology. The severity of the inflammatory reaction was assessed by evaluating the number of polymorphonuclear leukocytes per airway. Wet-to-dry-weight ratios were measured in the other lung. In Group 2, RL, delta N2/L, residual volume, and CC increased, whereas Cdyn decreased after acid inhalation; Cdyn and delta N2/L remained significantly different at the end of the experiment. Bilateral vagotomy, carried out in 5 dogs from each group, did not alter the acid-induced effects in Group 2. There was no difference between groups in wet-to-dry weight ratios. Group 2 had a more severe inflammatory reaction in the peripheral airways than Group 1 (p less than 0.025). We conclude that minimal, acute peripheral airway inflammation is associated with detectable abnormalities in small airway function.

Density-dependence of maximal expiratory flow was measured in 110 patients prior to resection for peripheral coin lesions. The resected lung or lobe was examined morphologically and graded for emphysema, membranous bronchiolitis, and respiratory bronchiolitis. Density dependence did not decrease with increasing airway obstruction, and there was no relationship between density-dependence and peripheral airway abnormality or emphysema in the group as a whole. When patients were arbitrarily divided into those with forced expiratory volume in one second (FEV1) greater than 80% predicted (n = 80) and FEV1 less than 80% predicted (n = 30), density-dependence correlated significantly and negatively with membranous bronchiolitis in those with FEV1 greater than 80% predicted and significantly but positively in those with more advanced airway obstruction. We conclude that density-dependence of maximal expiratory flow is not an accurate predictor of peripheral airway abnormality in patients with mild to moderate air-flow obstruction.

To determine whether clinical symptoms and pulmonary function abnormalities were more common in lifetime nonsmoking grain elevator workers exposed to grain dust than in lifetime nonsmoking community control subjects who were not occupationally exposed to dust, we obtained an occupational health questionnaire, spirometric variables, and flow-volume curves on 90 lifetime nonsmoking grain workers and 90 lifetime nonsmoking community control subjects. For these groups we calculated the prevalence of chronic bronchitis, defined as daily production of phlegm for 3 months/yr for at least 2 yr. The prevalence of chronic bronchitis was higher in nonsmoking workers (23.1%) than in nonsmoking control subjects (3.3%) (p less than 0.01). Nonsmoking grain workers had lower mean values than did nonsmoking control subjects for maximal mid-expiratory flow rate (p less than 0.01) and for maximal expiratory flow at 50% of vital capacity (p less than 0.01). We conclude that exposure to grain dust inlifetime nonsmoking grain workers is associated with an increased prevalence of chronic bronchitis and evidence of airflow obstruction.

Closing volume and closing capacity were determined in 82 working Appalachian coal miners and in a comparable group of control subjects. Abnormalities of closing volume and closing capacity were related to other measurements of pulmonary function. The relationship of smoking history, dust exposure, and presence of pneumoconiosis and bronchitis to elevations of closing volume and closing capacity was determined. It was shown that nonsmoking miners had elevated closing volume and closing capacity when compared to control subjects. Miners who were smokers or ex-smokers also had elevated closing capacity when compared to control subjects. Neither bronchitic symptoms nor the radiographic presence of pneumoconiosis were associated with an elevation of closing volume or closing capacity.