Airway function in lifetime-nonsmoking older asbestos workers

Previous studies of lung function in asbestos workers have documented airflow limitation in many of the workers, but the specific influence of asbestos exposure could not be clearly differentiated from the effects of the cigarette smoking habit. In this study, airway function was evaluated in lifetime-nonsmoking, long-term workers of the mines and mills of Québec. The 17 asbestos workers in this study had worked for an average of 28 years in the mines and mills of the local asbestos industry and did not have any other respiratory industrial dust exposure. They did not have a history of previous pulmonary disease and did not meet the usual diagnostic criteria for chronic bronchitis, emphysema, or asthma. Seven of the workers met the diagnostic criteria for asbestosis and 10 workers did not. The latter group of workers did not differ from a matched control group except in terms of a higher isoflow volume (p less than 0.05). The workers with asbestosis, however, had a restrictive pattern of lung function, increased isoflow volume, and increased upstream resistance at low lung volumes (p less than 0.01). Lung biopsy in three of the patients with the disease demonstrated peribronchiolar alveolitis and fibrosis with obliteration and narrowing of the small airways. These data on lifetime-nonsmoking, long-term asbestos workers provide further evidence of small airway obstruction associated with asbestos exposure and independent of the smoking habit. This airflow limitation was observed predominantly in workers with a restrictive pattern of lung function associated with peribronchiolar alveolitis. The lifetime-nonsmoking asbestos workers without restrictive patterns of lung function had minimal dysfunction of the peripheral airways.     

Lung function and respiratory health of long-term fiber-exposed stonewool factory workers.

The present study was undertaken to examine the respiratory health of a Danish workforce exposed to man-made vitreous fibers (MMVF) during production. Workers with more than 5 yr occupational exposure to MMVF (n = 377) were compared to a group without MMVF exposure (n = 381). Respiratory health was assessed by questionnaire, dynamic spirometry, and measurement of transfer factor. Overall response rate was 63%. A sample of nonresponders was assessed by questionnaire and spirometry. On most spirometric indices the two groups had comparable values. However, a larger proportion (14.5%) of the exposed subjects had an obstructive flow pattern compared with the control subjects (5.3%). Subgroup analyses showed that the elevated risk of airways obstruction associated with exposure was restricted to heavy smokers. Transfer factor and prevalences of symptoms and self-reported disease were similar in the two groups. There is no indication of excess risk of lung fibrosis. However, a number of exposed workers have some degree of airflow obstruction, which cannot be explained by known confounders. An additive or synergistic action between smoking and fiber exposure on airflow obstruction can be speculated.     

Cigarette smoke makes airway and early parenchymal asbestos-induced lung disease worse in the guinea pig

In order to assess the effects of cigarette smoke and asbestos exposure, we divided guinea pigs into 4 groups: smoking or nonsmoking, and asbestos-exposed or not asbestos-exposed groups. Asbestos-exposed animals were given a single intratracheal instillation of 5 mg UICC amosite, a dose and method of administration that we have previously shown produces morphologic changes in the small airways as well as minimal interstitial fibrosis. Animals were smoked 5 days per week for 6 months. By itself, smoking did not affect lung collagen content, small airways wall thickness, or the volume fraction of tissue surrounding airways, but it did cause a significant increase in alveolar mean linear intercept (Lm). Asbestos alone increased collagen content, airway wall thickness, and tissue volume fraction surrounding airways, the latter measure used to assess interstitial fibrosis. An unexpected finding was that asbestos also increased Lm. The two agents administered together caused more severe changes of all types than were produced by either agent alone, and the interaction between the 2 was generally synergistic. Smoke-exposed animals retained 3 times the asbestos fiber burden of those not smoke-exposed; the increase in retention was greater for short than for long fibers. We conclude that cigarette smoke can potentiate the fibrosis induced by asbestos, possibly because of increased fiber retention. As well, in this model, asbestos or asbestos plus cigarette smoke produces increases in alveolar size.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alveolitis of pulmonary asbestosis. Bronchoalveolar lavage studies in crocidolite- and chrysotile-exposed individuals

Bronchoalveolar lavage (BAL) findings in 27 individuals with crocidolite- or chrysotile-induced asbestosis were compared to BAL findings in 29 unexposed control subjects. Alveolitis, defined as an increase in the proportions and/or absolute numbers of inflammatory cells present in BAL fluid compared to values in control subjects, was present in 26 (96 percent) subjects with asbestosis. Most exhibited a neutrophil-eosinophil alveolitis, with neutrophil proportions increased to 7.4 +/- 0.7 percent and eosinophil proportions increased to 2.2 +/- 0.4 percent, compared to 2 +/- 0.5 percent and 0.4 +/- 0.01 percent, respectively, in control subjects (p less than 0.01 for both neutrophils and eosinophils). An increase in the total number of neutrophils and eosinophils per ml of lavage fluid was also seen (neutrophils 23 +/- 5 and eosinophils 13 +/- 4 per ml; p less than 0.05 compared to control subjects). Severity of the alveolitis, defined by the neutrophil or eosinophil proportions, was independent of a history of exposure to cigarette smoke. The pattern and severity of alveolitis in crocidolite- and chrysotile-induced asbestosis were similar. There was a significant correlation between duration of exposure to asbestos and neutrophil proportions (p less than 0.01). No significant difference in the severity of the alveolitis was observed between individuals with radiologic and physiologic evidence of asbestosis compared to those with asbestos exposure and crackles alone, suggesting that, in asbestosis as in other chronic interstitial lung diseases, radiologic and physiologic parameters do not reflect the severity of the alveolitis. This study demonstrates that a neutrophil-eosinophil alveolitis is present in individuals with crocidolite- and chrysotile-induced asbestosis, that this alveolitis is independent of cigarette smoking, and that the severity of the BAL changes is not reflected in radiologic and physiologic changes.     

Lymphocyte-macrophage alveolitis in nonsmoking individuals occupationally exposed to asbestos.

A disordered immunologic activity has been observed in humans and animal models of asbestosis and silicosis. To characterize the lung immunologic response following long-term occupational exposure to asbestos, bronchoalveolar lavage (BAL) was performed on 28 nonsmoking individuals. Increased BAL lymphocytes were observed in one third. Lung lymphocytes were predominantly of the CD4+ helper-inducer subtype with increased CD4+/CD8+ ratio and increased surface expression of DR antigen consistent with the activation phenotype. Histologic evaluation of lung tissue from two individuals with lymphocytic-macrophage alveolitis and asbestos exposure revealed an infiltration of alveolar walls with chronic inflammatory mononuclear cells (lymphocytes). Interferon gamma was spontaneously released by BAL cells from 19 (76 percent) of 25 of the individuals with asbestos exposure and only one of ten normal controls. The release of interferon gamma by BAL cells could be further stimulated with concanavalin A and suppressed by cyclosporine. Although asbestosis is characterized by a predominant alveolar macrophage alveolitis, there is a subgroup with lymphocytic alveolitis and activated lymphocytes participating in the inflammatory response, especially in those without respiratory impairment early in the course of the disease process.     

Spirometry, rapid FEV1 decline, and lung cancer among asbestos exposed heavy smokers

We assessed whether spirometric measurements are associated with the development of accelerated FEV(1) decline and lung cancer among active and previous smokers with a wide range of lung function. Bivariate and multivariate analyses that adjusted for age, intervention arm, smoking status at enrollment and smoking history, years exposed to asbestos, and evidence of asbestosis were used to assess whether baseline FEV(1) and FEV(1)/FVC ratio were associated with accelerated FEV(1) decline and incident lung cancer. The 3,041 participants enrolled from 1985 to 1994 were followed through April 30, 2005. Baseline FEV(1)/FVC ratio<0.7 was significantly associated with an increased risk for rapid lung function decline (OR=1.73; 95% CI 1.31-2.28; p<0.001). Baseline FEV(1)/FVC ratio<0.7 was also significantly associated with an increased risk of developing lung cancer, even when baseline FEV(1) was >80%. Lung cancer risk among participants with baseline airflow obstruction and FEV(1)<60% was 4-fold higher than participants without baseline airflow obstruction and FEV(1)>80% (p<0.001), even among former smokers. These data indicate an FEV(1)/FVC<0.7 among smokers is significantly associated with faster airflow loss, and an increased risk for developing lung cancer, even among those individuals with a normal FEV(1).     

The effect of bronchoalveolar lavage on bronchial responsiveness in patients with airflow obstruction

This study assessed the effect of bronchoalveolar lavage (BAL) on nonspecific bronchial responsiveness in 31 patients. Of these, 20 had airflow obstruction; 11 control subjects had normal pulmonary function. Bronchial responsiveness to methacholine, expressed as the dose of inhaled methacholine required to provoke a 20 percent fall in forced expiratory volume in one second (PD20 FEV1), was measured before and after BAL. We found no evidence for the induction of responsiveness by BAL in 11 control subjects with negative methacholine tests prior to the procedure. There were small but significant falls in FEV1 following BAL in both the control group and in patients with airflow obstruction. Thus, BAL does not appear to induce nonspecific bronchial hyperresponsiveness in subjects without airflow obstruction, nor does it affect airway responsiveness in emphysema patients. Among asthmatics, bronchial responsiveness can be increased as a result of BAL; this increase was greatest in patients who were most responsive initially.     

Pulmonary function and peripheral airway disease in patients with mineral dust or fume exposure

Cigarette smoking and mineral dust exposure combined result in small airways function abnormalities difficult to distinguish from smoking effects alone. To determine if mineral dust or fume exposure in smokers results in additional changes in small airways structure and function, we studied small airways disease and pulmonary function in 25 persons (62.4 +/- 8.8 yr) with exposure to mineral dust or fume for 10 yr or more and compared them individually with control subjects without dust exposure (61.8 +/- 8.5 yr) matched for age, smoking history, and lobe resected. All subjects were patients undergoing surgical resection for isolated coin lesions. Occupational histories and measurements of lung volumes, flow rates, small airways function, diffusing capacity, and pressure-volume relationships were obtained preoperatively. Membranous bronchioles were graded for the presence and degree of mural inflammation, fibrosis, muscle, pigment, and squamous and goblet cell metaplasia. Respiratory bronchioles were similarly graded for inflammation, fibrosis, muscle, pigment, and lumenal macrophages. The dust-exposed group had increased fibrous tissue deposition and goblet cell metaplasia in the membranous bronchioles (p less than 0.05). When the exposed group was divided according to occupation into miners (n = 13) and nonminers exposed in other dusty jobs (n = 12), the pathologic changes were evident in both exposed groups. No differences in pulmonary function were seen between the 2 groups. We conclude that occupational exposure to mineral dust and fume produces structural changes in peripheral airways that are greater than those seen with smoking alone, but these changes were not associated with a greater deterioration in lung function.     

Alveolar macrophages from patients with asbestos exposure release increased levels of leukotriene B4

The alveolar influx and subsequent activation of inflammatory cells such as neutrophils and eosinophils are believed to be important in the pathogenesis of many interstitial lung disorders, including asbestosis. Indices of lower respiratory tract abnormalities detected by bronchoalveolar lavage (BAL) were investigated in 93 asbestos-exposed workers as well as in smoking (n = 12) and nonsmoking (n = 10) control subjects. Patients with clinical asbestosis (n = 12) exhibited increases in both BAL neutrophils and BAL eosinophils, expressed as both percentage of total cells and total numbers, when compared to asbestos-exposed workers without asbestosis (n = 81) and control subjects. Significantly greater numbers of BAL neutrophils were also found in asbestos-exposed workers without asbestosis than in either smoking or nonsmoking control subjects. These abnormalities correlated significantly with in vitro BAL alveolar macrophage production of the potent leukocyte chemotaxin, leukotriene B4 (LTB4). For example, basal, unstimulated LTB4 production was 3.1 +/- 0.8 ng/10(6) alveolar macrophages for patients with asbestosis, 1.05 +/- 0.2 ng/10(6) cells in asbestos workers without asbestosis, 0.9 +/- 0.2 ng/10(6) cells in control nonsmokers, and 0.2 +/- 0.05 ng/10(6) cells in control smokers. Stimulated LTB4 release from BAL alveolar macrophages (A23187 or arachidonate) was even more pronounced in asbestos workers with or without asbestosis, suggesting an in vivo priming effect on alveolar macrophage synthesis of LTB4. Cell-free BAL supernatants from asbestos-exposed patients with or without asbestosis also contained significantly greater amounts of LTB4 than did those from control subjects, indicating enhanced in vivo production of this inflammatory mediator.(ABSTRACT TRUNCATED AT 250 WORDS)     

Small airways disease and mineral dust exposure. Prevalence, structure, and function

Previously we described a lesion of the small airways that appears related to mineral dust exposure and is found in asbestos and nonasbestos dust-exposed populations. To determine the usefulness of this lesion as a marker for mineral dust exposure, and to determine whether it produces functional consequences, we examined a group of 53 workers who had been either hard rock miners or in the asbestos, construction, and shipyard industries. The specific lesion (mineral dust airways disease (MDAD] consists of marked fibrosis and pigmentation of the respiratory bronchioles and was found in 13 of 53 workers with dust exposure, but only in 1 of 121 without dust exposure. Compared with age and smoking-matched dust-exposed control subjects, patients with this lesion had significant abnormalities of forced expiratory volume in one second (FEV1), forced expiratory flow during the middle half of the forced vital capacity (FEF25-75), vital capacity (VC), and nitrogen washout. In addition to fibrosis in the walls of respiratory bronchioles, these patients also had significant increases of fibrosis in the walls of membranous bronchioles, indicating that changes in the small airways are widespread in this subset of workers. We conclude that markedly abnormal small airways are present in some workers with mineral dust exposure; pathologic observation of this lesion is a good indicator of dust exposure, and its presence is associated with abnormalities of air flow greater than those induced by smoking alone. The presence of this lesion in only a portion of dust-exposed workers may account for contradictory results in past studies that attempted to demonstrate air flow abnormalities associated with mineral dust exposure.     

Pathophysiologic correlations in asbestos-induced airway disease in the guinea pig

To determine whether asbestos-induced changes in the structure of the walls of small airways might be associated with abnormalities of pulmonary function, guinea pigs were given 10 mg of amosite asbestos (test group) or saline (control group) by intratracheal instillation. Pulmonary function tests performed 6 months later revealed significant increases in FRC, RV, and TLC in the test group. Measurement of airway wall thickness showed that both membranous and respiratory bronchioles were significantly thickened in the test group; this group also had airways of smaller internal diameter than the controls. Analysis for lung collagen content as hydroxyproline showed a 50% increase in the asbestos exposed animals. There was, however, only minimal and very focal interstitial fibrosis (asbestosis) in the lung parenchyma. Analysis of fiber size indicated that the fibers obtained by digestion of the tissue or from the lavage fluid were significantly longer and wider than those in the original asbestos sample; however, the tissue contained considerably larger fibers than the lavage fluid. We conclude that: Asbestos can produce airway fibrosis and narrowing causing air trapping on pulmonary function examination; this process occurs in the absence of significant interstitial fibrosis of the parenchyma (asbestosis), implying that abnormalities of pulmonary function which are consistent with airflow obstruction in asbestos exposed animals can be caused by pathologic changes in the small airways alone; long asbestos fibers are preferentially retained in the lung, and the longest fibers appear to be in a compartment inaccessible to lavage, presumably, in this model, in airway walls. Enhanced penetration of long fibers into tissue may be one reason why long fibers are more pathogenic than short ones.     

Sequential bronchoalveolar lavage in experimental extrinsic allergic alveolitis. The influence of cigarette smoking

We studied the alterations induced by acute experimental extrinsic allergic alveolitis (EAA) on bronchoalveolar cell population in smoking and nonsmoking guinea pigs. Sixty-two animals divided into 3 groups were studied: Group 1 (17 animals), controls; Group 2 (21 animals), extrinsic alveolitis; Group 3 (24 animals), cigarette smoking and alveolitis. Bronchoalveolar lavages (BAL) were performed on Days 1, 19, and 44 for all animals. Group 3 animals had a fourth lavage before starting cigarette smoking, that is, 28 days before the beginning of the antigen injections. The other lavages were as for the other groups. BAL results on Day 1 were similar for each group. Cigarette smoking per se did not modify BAL in Group 3. EAA induction resulted in a large increase in all BAL cells, especially neutrophils of recovered fluid, which increased from 38 x 10(3) to 1,474 x 10(3) ml-1 (p less than 0.01) in Group 2 and from 58 x 10(3) to 740 x 10(3) in Group 3 (p less than 0.01). After maintenance, BAL neutrophils.ml-1 decreased to 444 x 10(3) in Group 2 (p less than 0.01), but stayed the same in Group 3: 973 x 10(3). After EAA induction, BAL neutrophils.ml-1 were higher in Group 2 than in Group 3 (p = 0.039); however, Group 2 had less neutrophils.ml-1 than Group 3 (p = 0.035) after EAA maintenance. We conclude that EAA results in a neutrophilic alveolitis and which can be evaluated by sequential BAL, and that cigarette smoking decreases the initial neutrophilic response and retards the eventual recovery during maintenance injections.     

The health impact of undiagnosed airflow obstruction in a national sample of United States adults

To determine the health and functional impact of undiagnosed airflow obstruction for subjects in the general population, we used data obtained as part of the Third National Health and Nutrition Examination Survey (NHANES III). Categories of diagnosed and undiagnosed airflow obstruction were defined using questionnaire responses and spirometric results. Health and functional impact of airflow obstruction was assessed from responses to questions about general health status, walking 1/4 mile, lifting or carrying something as heavy as 10 lb, or needing help with personal care. Undiagnosed airflow obstruction (12.0%) was more common than doctor-diagnosed chronic obstructive pulmonary disease (COPD) (3.1%) or asthma (2.7%). Although undiagnosed airflow obstruction was usually very mild, approximately 5% of the entire sample had an FEV(1) less than 75% predicted. After adjusting for smoking, obesity, and comorbid conditions, the risk of impaired health and functional status with undiagnosed airflow obstruction was independently associated with severity of FEV(1) impairment. For males and females, ever smoking was strongly associated with all types of airflow obstruction, diagnosed or not. However, among females with airflow obstruction, 12.2% to 35.2% never smoked. Undiagnosed airflow obstruction is common in the general population of the United States and is associated with impaired health and functional status. Keywords: airflow obstruction; spirometry; health impact; screening     

Lung function in patients with tracheobronchopathia osteochondroplastica

We have analysed the ventilatory function of seven patients with tracheobronchopathia osteochondroplastica. One patient showed reversible airflow obstruction meeting the criteria of bronchial asthma. Another two patients yielded reduced percentage forced expiratory volume (FEV%) and features of small airways obstruction. The patients' previous spirometric measurements also made the rough estimation of longitudinal changes in lung function possible during a follow-up period of 1-8 yrs (mean 4.2 yrs). Although most patients had suffered severe chest infections, no deterioration in spirometric parameters was found during the follow-up. These findings suggest that tracheobronchopathia osteochondroplastica usually has a benign course.     

Respiratory rate during acute asthma

Asthmatic patients hyperventilate during acute attacks, but controversy persists as to whether they breathe rapidly, deeply or both. We monitored respiratory rate under the three following conditions: (1) asthma treated in the emergency room; (2) airways obstruction provoked by methacholine inhalation; and (3) airways obstruction provoked by exercise. In 47 acutely ill asthmatic patients, respiratory rate was higher than in 42 nonasthmatic control patients in the emergency room. Pretreatment respiratory rate correlated with peak expiratory flow rate and forced expired volume in one second. In 17 asthmatic patients and 16 healthy volunteers, breathing pattern was monitored by respiratory inductance plethysmography. Methacholine inhalation and exercise provoked significant airways obstruction in asthmatic patients but not in control subjects. In asthmatic patients, minute ventilation and tidal volume increased above that of control subjects following methacholine and exercise, but the rate was no higher than in control subjects. We conclude that the respiratory rate is increased in naturally occurring asthma, but not when acute airways obstruction is induced transiently in the laboratory. In the former setting, the respiratory rate is correlated with spirometric measures of airflow obstruction, but the weakness of the correlation does not allow the respiratory rate to be used as a substitute for spirometry.     

Asbestos exposure and retention as determinants of airway disease and asbestos alveolitis

To evaluate the relationships of asbestos exposure, retention, airway response, and the asbestos alveolitis, we exposed 2 groups of sheep every 2 wk for 3 yr to either 100 ml phosphate-buffered saline (PBS) or 100 mg UICC chrysotile fibers in 100 ml PBS. The sheep were evaluated periodically by pulmonary function tests (PFT), chest radiograph (CR), bronchoalveolar lavage (BAL), and transbronchial lung biopsy (TLB). At Month 24 of the study, all asbestos-exposed sheep had significant increases in lung resistance and upstream resistance. However, only 9 of the 16 asbestos-exposed sheep had significant changes in TLB, CR, Cst, and VC, which clearly separated them from the other 6 sheep in these parameters. The 2 groups, however, had similar air-flow limitation. At lung biopsy, all asbestos-exposed sheep had significant peribronchiolar fibrosis, with significant alveolitis only in the group of 9 sheep with radiographic and functional changes of early asbestosis. The 9 sheep also had significant changes in BAL cellularity and biochemical profile, which differentiated them from the other 6 asbestos-exposed sheep. Analysis of BAL fiber content at that point revealed that despite identical exposure, the group with interstitial lung disease had significantly more fiber retention (p less than 0.01). The data demonstrate that whereas asbestos airway disease appears to be primarily an exposure-dose-related response, the lung response appears to be more closely related to alveolar retention of the dust.     

Small airway function improvement after smoking cessation in smokers without airway obstruction

OBJECTIVE: Studying smokers with normal spirometry requires monitoring tools of the peripheral lung. A validated multiple breath washout technique was used to assess possible recovery of smoking-induced small airway malfunction in acinar and conductive lung zones. METHODS: Eighty-seven smokers with a smoking history of at least 10 pack-years but absence of spirometric airflow obstruction were invited for assessment of lung function and small airway function at baseline and after 1 wk, 3 mo, 6 mo, and 12 mo of smoking cessation. A control group of 16 persistent smokers was studied at the same time intervals. MEASUREMENTS AND MAIN RESULTS: Of the 87 smokers, 66, 32, 28, and 21% successfully ceased smoking for 1 wk, 3 mo, 6 mo, and 12 mo, respectively. Lung function parameters remained essentially unaffected by smoking cessation. Ventilation heterogeneity showed transient improvements after 1 wk in the acinar lung compartment with a return to baseline afterwards. By contrast, there were persistent improvements in the conductive airway compartment; for example, smokers who successfully quit smoking for 12 mo (n=18) showed a 30 and 42% reduction of conductive airways abnormality after 1 wk and 1 yr, respectively. CONCLUSIONS: Smokers with early signs of small airway malfunction who successfully quit smoking show sustained improvements of conductive airway malfunction. In contrast, acinar airway malfunction quickly returns to baseline after a transient improvement.     

Analysis of airflow obstruction by bronchoalveolar lavage following bone marrow transplantation. Implications for pathogenesis and treatment

The development of airflow obstruction, most often due to bronchiolitis, is a significant cause of morbidity and mortality in recipients of allogeneic BMT. Current consensus holds that this airways disease is the result of chronic GVHD and/or CMV infection. However, recent studies of idiopathic forms of BRO have demonstrated a striking influx of neutrophils into the lungs of affected individuals. Reasoning that the immune cell populations involved in tissue injury associated with either CGVHD or CMV infection would consist predominantly of lymphocytes, we tested this hypothesis by performing BAL in 12 adults with minimal or absent smoking histories who developed significant airflow obstruction (FEV1/FVC = 80.7 +/- 1 percent preBMT and 56.8 +/- 2.4 percent postBMT; p less than 0.001) following allogeneic BMT. Eleven of 12 patients had evidence of chronic, stable GVHD at the time of the study. In contrast to non-BMT patients with BRO, BAL defined two distinct patterns of lung inflammation in the BMT patients with airflow obstruction: (a) neutrophil predominance (five patients; neutrophil percentage = 20.2 +/- 6.6 percent); and (b) lymphocyte predominance (three patients; lymphocyte percentage = 35.9 +/- 12.1 percent). These data suggest that the pattern of inflammation in the lungs of BMT patients with BRO is not uniform and is not associated with active microbial infection. From these results, it is inferred that the airways injury in BMT patients may reflect diverse pathogenetic mechanisms initiated in the context of CGVHD and cytotoxic drug therapy.     

A prospective evaluation of plain radiographic signs of chronic obstructive pulmonary disease.

Plain film signs of COPD, spirometric evidence of airflow obstruction, and smoking history were correlated in a group of 182 men aged 32 to 85 years (average, 57.5 years) who presented for evaluation of possible pulmonary disability. There were 148 current or past smokers (range, 0.66 to 150 pack-years; average, 31.89 pack-years) and 34 lifetime nonsmokers. A single observer, who had no knowledge of the other parameters, prospectively evaluated posteroanterior chest radiographs for 11 signs of COPD. Airflow obstruction was defined as a reduction in FEV1/FVC% below the 95% confidence limit of normal. Obstruction was classified on the basis of the reduction in FEV1 as mild (FEV1 greater than 2.5L), moderate (FEV1 greater than 1.0 L and less than 2.5 L), or severe (FEV1 less than 1.0 L). Spirometric evidence of airflow obstruction was present in 67 patients; obstruction was mild in 26, moderate in 36, and severe in 5. We found a statistically significant association between smoking and airflow obstruction on spirometry (P less than 0.001) and an equally significant association between smoking and radiographic signs of COPD on plain chest films (P less than 0.001). Both airflow obstruction and radiologic signs of COPD were generally absent in lifetime nonsmokers. The plain film signs of COPD were only of moderate value in predicting spirometric evidence of airflow obstruction in smokers; spirometric evidence is not the gold standard for the presence of COPD, however, and the strong association between smoking and these radiologic signs may indicate that in smokers the presence of plain film signs of COPD reflects morphologic abnormality in the lungs indicative of disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation and management of scleroderma lung disease using bronchoalveolar lavage

PURPOSE: Bronchoalveolar lavage (BAL) was performed in 43 nonsmoking patients with scleroderma (systemic sclerosis) to determine the frequency of alveolitis, the status of BAL findings over time, and the relationship of such findings to pulmonary status initially and at follow-up. PATIENTS AND METHODS: Forty-three nonsmoking patients with systemic sclerosis underwent extensive pulmonary evaluation including pulmonary function tests, chest radiographs, and BAL with analysis of cells, IgG, albumin, immune complexes, and fibronectin. RESULTS: Alveolitis was detected on initial BAL evaluation in 21 patients (49%). Alveolitis was characterized by hypercellular lavage fluid, due to an absolute increase in alveolar macrophages and due to an increase in both the absolute number and percentage of granulocytes (neutrophils and eosinophils). Patients with systemic sclerosis had significantly higher levels of IgG and immune complexes in BAL fluid than did control subjects, and alveolar macrophages from patients with systemic sclerosis released higher amounts of fibronectin in vitro. In serial studies, alveolitis was found to persist. Patients with alveolitis had greater dyspnea than patients without alveolitis (p = 0.02), and they had greater reductions in lung volumes and carbon monoxide diffusing capacity (DLCO) (p = 0.004). Furthermore, patients with persistent alveolitis had significantly greater reductions in pulmonary function over time than patients without alveolitis (forced vital capacity [FVC]: -0.69 L versus -0.05 L, p less than 0.001; DLCO: -2.94 mL/minute/mm Hg versus +0.16 mL/minute/mm Hg, p = 0.03). BAL was used to select patients with alveolitis and at risk of pulmonary deterioration, and treatment was instituted with cyclophosphamide and prednisone, resulting in significant improvement in dyspnea (p less than 0.001) and the rate of change of FVC (p = 0.02) and DLCO (p less than 0.001). CONCLUSION: We conclude that alveolitis occurs frequently in systemic sclerosis and that BAL is useful in identifying such patients who are at risk for a further decline in pulmonary status. Preliminary observations suggest that treatment of patients with active alveolitis may result in improvement in pulmonary status.