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Objectives: To compare the distribution of lung volume at total lung capacity (TLC) among adult men and women known to have normal lung function or chronic obstructive disease or restrictive lung disease (RLD)., Design: Five-year retrospective study., Setting: Review of available clinical pulmonary function testing (PFT) reports and chest radiographs., Patients: Sixty-four patients presenting with normal PFT and chest radiograph findings (normal subjects), 26 patients with severe COPD and increased TLC (COPD group), 29 patients with cystic fibrosis (CF) and increased TLC (CF group), and 19 patients with RLD with a clinical diagnosis of pulmonary fibrosis and a reduced TLC (RLD group)., Measurements: Average posteroanterior rib cage diameter (PAave), average lateral rib cage diameter (LAave), and average vertical height of the diaphragm (HDIave) were measured using radiography. Normal prediction equations were generated based on stature, body mass index (BMI), age, and sex as independent variables and then used in between-group comparisons., Results: PAave correlated positively with BMI and age but not with height, whereas LAave correlated positively with BMI and height but not with age. HDIave correlated positively with height and age but negatively with BMI. PAave and LAave were smaller and HDIave was greater in women than men having the same stature. In the COPD group and in male CF group patients, BMI was low and only HDIave was greater than in sex-, age-, and height-matched normal subjects, but in female CF group patients, only the rib cage diameters were greater than normal. In the RLD group, PAave and HDIave were smaller than predicted and inversely related to each other, but LAave was normal., Conclusion: Variations in maximum lung volume caused by gender, growth, or by lung diseases are nonisotropic and entail substantial changes in chest wall shape.

The role of infection in exacerbations of COPD remains controversial and incompletely understood. Although some investigators believe that bacteria are not important for patients with exacerbation, we disagree and believe that patients with at least two of the three cardinal symptoms of exacerbation should receive antibiotic therapy. With an open-minded view of the area, we review the data, showing that bacteriologic studies, pathologic investigations, and clinical trials all support roles for bacteria and antibiotic therapy in this disease. Still, many questions remain, and future studies will be needed to better define the mechanisms of bacterial invasion in the bronchitic patient and to develop effective vaccines to prevent exacerbations. In the meantime, we must rely on antibiotic therapy, and we will need prospective studies to corroborate preliminary findings showing that different patients may require different therapies; thus, patient subsetting may be vital in the selection of antibiotic therapy for exacerbations of COPD.

Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants and/or a depletion of antioxidants. Oxidative stress is thought to play an important role in the pathogenesis of a number of lung diseases, not only through direct injurious effects, but by involvement in the molecular mechanisms that control lung inflammation. A number of studies have shown an increased oxidant burden and consequently increased markers of oxidative stress in the airspaces, breath, blood, and urine in smokers and in patients with COPD. The presence of oxidative stress has important consequences for the pathogenesis of COPD. These include oxidative inactivation of antiproteinases, airspace epithelial injury, increased sequestration of neutrophils in the pulmonary microvasculature, and gene expression of proinflammatory mediators. With regard to the latter, oxidative stress has a role in enhancing the inflammation that occurs in smokers and patients with COPD, through the activation of redox-sensitive transcriptions factors such as nuclear factor-kappaB and activator protein-1, which regulate the genes for proinflammatory mediators and protective antioxidant gene expression. The sources of the increased oxidative stress in patients with COPD are derived from the increased burden of oxidants present in cigarette smoke, or from the increased amounts of reactive oxygen species released from leukocytes, both in the airspaces and in the blood. Antioxidant depletion or deficiency in antioxidants may contribute to oxidative stress. The development of airflow limitation is related to dietary deficiency of antioxidants, and hence dietary supplementation may be a beneficial therapeutic intervention in this condition. Antioxidants that have good bioavailability or molecules that have antioxidant enzyme activity may be therapies that not only protect against the direct injurious effects of oxidants, but may fundamentally alter the inflammatory events that play an important part in the pathogenesis of COPD.

A common feature of COPD and other chronic lung diseases is hypersecretion of mucus into the airways, causing peripheral airway plugging and further airflow obstruction. The mucus is secreted by goblet cells, which are present in excessive numbers in COPD. This review describes how neutrophils in the airways of COPD patients stimulate the goblet cells to secrete their products. Recent findings on the mechanisms of neutrophil stimulation of goblet cell degranulation are discussed. These implicate the proteolytic enzyme elastase and cell surface adhesion molecules, and provide a basis for the investigation of potential novel therapies.

Background: A central feature in the pathogenesis of COPD is the inflammation coexisting with an abnormal protease/antiprotease balance. However, the possible role of different serine and metalloproteinases remains controversial., Patients and Measurements: We examined the expression of gelatinases A and B (matrix metalloproteinase [MMP]-2 and MMP-9); collagenases 1, 2, and 3 (MMP-1, MMP-8, and MMP-13); as well as the presence of apoptosis in lung tissues of 10 COPD patients and 5 control subjects. In addition, gelatinase-A and gelatinase-B activities were assessed in BAL obtained from eight COPD patients, and from six healthy nonsmokers and six healthy smoker control subjects., Setting: Tertiary referral center and university laboratories of biochemistry, and lung cell kinetics., Results: Immunohistochemical analysis of COPD lungs showed a markedly increased expression of collagenases 1 and 2, and gelatinases A and B, while collagenase 3 was not found. Neutrophils exhibited a positive signal for collagenase 2 and gelatinase B, whereas collagenase 1 and gelatinase A were revealed mainly in macrophages and epithelial cells. BAL gelatin zymography showed a moderate increase of progelatinase-A activity and intense bands corresponding to progelatinase B. In situ end labeling of fragmented DNA displayed foci of positive endothelial cells, although some alveolar epithelial, interstitial, and inflammatory cells also revealed intranuclear staining., Conclusion: These findings suggest that there is an upregulation of collagenase 1 and 2 and gelatinases A and B, and an increase in endothelial and epithelial cell death, which may contribute to the pathogenesis of COPD through the remodeling of airways and alveolar structures.

Study Objectives: To study the flow-volume loop for evidence of variable extrathoracic airflow obstruction in Persian Gulf War veterans., Design: Retrospective case-control, single-center study., Setting: The pulmonary division of an academic health-care center., Subjects: A convenience sample of the Persian Gulf Registry., Measurements and Interventions: (1) Midvital capacity ratio (ratio of maximum forced midexpiratory to maximum forced midinspiratory flow). This ratio is the criterion standard for the diagnosis of variable extrathoracic airflow obstruction. (2) Evaluation of the anatomy and function of the extrathoracic airway by fiberoptic bronchoscopy. (3) Further investigation into the airway abnormality by histologic evaluation of tracheal biopsy samples in Gulf War veterans only., Results: Midvital capacity was > 1.0 in 32 of 37 Gulf War veterans compared with only 11 of 38 control subjects. The mean (+/-SD) value was 1.37+/-0.4 among Gulf War veterans and 0.88+/-0.3 among control subjects (p=0.0000005). FVC and its ratio to FEV1 were normal in all these subjects. Bronchoscopy showed inflamed larynx and trachea in all (n=17) Gulf War veterans. Histologic study showed chronic inflammation of the trachea in everyone (n=12) who had an adequate biopsy sample., Conclusion: Physicians should be made aware of the presence of chronic inflammation of the upper airways and inspiratory airflow limitation in a number of Gulf War veterans.

Background: Reduced muscle aerobic capacity in COPD patients has been demonstrated in several laboratories by phosphorus magnetic resonance spectroscopy and by analysis of oxygen uptake (VO2) kinetics. COPD patients are usually elderly, hypoxemic, poorly active with muscle atrophy, and often malnourished. Under these conditions there is usually reduction of O2 delivery to the tissues (bulk O2 flow), redistribution of fiber type within the muscle, capillary rarefaction, and decreased mitochondrial function, alterations all capable of reducing muscle aerobic capacity. In COPD, the effect of reduced body mass on muscle aerobic capacity has not been investigated (to our knowledge)., Methods: We studied 24 patients with stable COPD with moderate-to-severe airway obstruction (68+/-5 [SD] years; FEV1, 39+/-12% predicted; PaO2, 66+/-8 mm Hg; PaCO2, 41+/-3 mm Hg) with poor to normal nutritional status, as indicated by a low-normal percent of ideal body weight (IBW). Each subject first underwent 1-min maximal incremental cycle ergometer exercise for determination of VO2 peak and lactate threshold (LT). Subsequently, they performed a 10-min moderate (80% of LT-VO2) constant load exercise for determination of oxygen deficit (O2DEF) and mean response time VO2 (MRT). VO2, CO2 output (VCO2), and minute ventilation were measured breath by breath., Results: Patients displayed low VO2 peak (1,094+/-47 [SE] mL/min), LT-VO2 (35+/-3% predicted O2 max), and higher MRT-VO2 (67+/-4 s). Univariate regression analysis showed that percent of IBW correlated with indexes of maximal and submaximal aerobic capacity: vs VO2 peak, R=0.53 (p<0.01); vs MRT R=-0.77 (p<0.001). Using stepwise regression analysis, MRT correlated (R2=-0.70) with percent of IBW (p<0.01) and with PaO2 (p<0.05)., Conclusions: Reduced body mass has an independent negative effect on muscle aerobic capacity in COPD patients: this effect may explain the variability in exercise tolerance among patients with comparable ventilatory limitation.

Background: The contribution and role of emphysema and small airways disease in causing expiratory airflow limitation in COPD is controversial., Methods: We obtained high-resolution thin-section 2-mm CT scans of the lung for emphysema grading and lung function in 116 consecutively seen COPD outpatients with fixed expiratory airflow limitation. In this group, inflated whole lung(s) were subsequently obtained in 24 patients (23 autopsy, 1 surgery) for morphologic studies and results compared with lung CT. Airway histologic condition was studied in 17 of the 24 patients., Results: There was fair to weak negative correlation between CT emphysema score and either FEV1/FVC percent (r = -0.51, p = 0.001) or FEV1 percent predicted (r = -0.31, p = 0.001). In only 24 of the 81 patients (30%) with FEV1 less than 50% predicted, the CT emphysema score was 60 or more, indicating severe emphysema. In the 24 patients studied, there was a good correlation (r = 0.86, p = 0.001) between CT and pathologic grade of emphysema. While respiratory bronchioles (RBs) and membranous bronchioles (MBs) demonstrated marked morphologic abnormalities, there was a weak correlation with emphysema grade (for RB, r = 0.36, p = 0.16; for MB, r = 0.41, p = 0.10) or with FEV1 percent predicted (for RB, r = -0.21, p = 0.42; for MB, r = -0.28, p = 0.28). There was no correlation between emphysema and FEV1 percent predicted (r = -0.13, p = 0.54)., Conclusions: High-resolution CT lung scans are an in vivo surrogate to quantitate moderate to severe morphologic emphysema. Emphysema does not appear to be primarily responsible for severe expiratory airflow limitation in most patients with severe COPD. There was no correlation between severity of small airway histologic condition and emphysema or FEV1 percent predicted. The causes of the lesions responsible for small airways obstruction need to be identified.

Monodisperse aerosol particles can be used to assess noninvasively intrapulmonary airspace dimensions. Since emphysematic changes in the peripheral lung are difficult to detect with most of the common lung function tests, aerosol-derived airway morphometry was used to assess the peripheral airspace dimensions (EAD800) in 25 patients with COPD and in 36 healthy volunteers. Spirometric and body plethysmographic measurements were performed in all patients. In ten patients, high-resolution CT-derived mean lung density (MLD) was additionally assessed. In healthy subjects, EAD800 was 0.39 +/- 0.05 mm. In patients, EAD800 was significantly increased (0.82 +/- 0.33 mm). In a subset of nine patients with severe alpha 1-antitrypsin deficiency and clinically severe emphysema, EAD800 was even larger (1.14 +/- 0.32 mm). In patients, EAD800 correlated with MLD (r = 0.82), diffusion capacity (DCO) (r = 0.78), and FEV1 (r = -0.75). Since MLD is considered a valid indicator for lung emphysema, the close correlation between EAD800 and MLD suggests that EAD800 reflects enlarged peripheral airspace dimensions in patients with emphysema.

In order to characterize the imbalance between proteinases and proteinase inhibitors in sputum sol phases, we studied 25 patients (mean age, 59 +/- 11 yr) with exacerbated chronic obstructive pulmonary disease (COPD). An aliquot of sputum was used for bacteriologic determinations, and the remainder was centrifuged in order to obtain gel and sol phases. On the basis of the bacteriologic data, patients were divided into colonized patients (14) and noncolonized patients (11). All of the major inhibitors were immunologically detectable in sol phases without a significant difference between colonized and noncolonized patients (alpha 1-proteinase inhibitor [alpha 1-PI], 2.56 microM +/- 0.53 microM and 2.39 microM +/- 0.72 microM; alpha 2-macroglobulin [alpha 2-MG], 0.21 microM +/- 0.07 microM and 0.16 microM +/- 0.05 microM; antileukoprotease (ALP), 1.78 microM +/- 0.57 microM and 1.53 microM +/- 0.6 microM, respectively [mean +/- SE]). With regard to proteinase activities, both free elastase-like and free chymotrypsin-like activities were detectable in the majority of patients (15/25) (0.59 microM +/- 0.15 microM and 0.74 microM +/- 0.15 microM for elastase-like activity [ELA], and 0.010 microM +/- 0.003 microM and 0.017 microM +/- 0.007 microM for chymotrypsin-like activity [CLA], respectively [mean +/- SE]). The inhibitory profile of proteinase activities, performed by means of a panel of inhibitors, allowed us to assign specific activities mainly to neutrophil elastase and cathepsin G (Cat G). Next we looked at the relationships between inhibitors and proteinase activities. We found a significant negative correlation between neutrophil elastase activity and ALP (r = -0.58; p < 0.01). In confirmation of this suggestion, sol phases were divided into samples (15) with detectable ELA (> 0.50 microM) and samples (10) with no detectable ELA (< 0.18 microM). Levels of alpha 1-PI and alpha 2-MG did not differ significantly between the two groups, whereas ALP values were higher in the group with no detectable ELA (3.12 microM +/- 0.69 microM) than in the other group (0.58 microM +/- 0.21 microM; p < 0.001). We conclude that most sputum sol phases from patients with exacerbated COPD have a high burden of free neutrophil elastase and Cat G. Antileukoprotease seems to be the major naturally occurring inhibitor effective in the modulation of proteinase activities in bronchial secretions under these conditions.

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.

Classification of chronic airflow obstruction may be based on the site of the obstructing lesions. It is seldom that only one type of lesion is present, but one may often dominate. In chronic bronchitis, the major disease of large airways, chronic mucus hypersecretion, is reflected by an increase in size of bronchial mucous glands. This may be a factor in airway narrowing, especially with coexisting edema of the airway wall. Excess intralumenal mucus compounds the obstruction. Increased airways reactivity is present in 15 to 70 percent of patients with chronic airflow obstruction. Increased airway muscle and cartilage atrophy are features of chronic bronchitis, but the association of increased muscle with increased airway reactivity is poor. Inflammation of the small airways (bronchiolitis) is a significant complication for cigarette smokers and is an important cause of mild chronic airflow obstruction. Goblet cell metaplasia is a reflection of chronic small airways inflammation and, together with intralumenal mucus, is an important feature. Permanent narrowing of the small airways presumably results from inflammation with consequent fibrosis, while functional narrowing results from release of mediators of inflammation. Increased muscle mass is present in some cases. Distortion and irregularity of small airways related to emphysema are major factors in severe obstruction. Lesser degrees of emphysema may be associated with a diminished number of alveolar attachments and mild chronic airflow obstruction. Emphysema, the dominant lesion in patients with severe chronic airflow obstruction, results from parenchymal lesions. Centrilobular emphysema, in which the respiratory bronchioles are selectively or dominantly involved, is the most common form.(ABSTRACT TRUNCATED AT 250 WORDS)

Two patients with ulcerative colitis developed progressive obstructive pulmonary disease. In one, the abnormality was a sclerosing peribronchiolitis confined to small airways, while the other demonstrated a large airway fibrotic obliterative bronchitis. A review of airway involvement in ulcerative colitis and a discussion of the possible similarity to another extraintestinal manifestation of ulcerative colitis, sclerosing cholangitis, are presented.

To assess the effect of COPD on diaphragm muscle dimensions, we measured diaphragm muscle mass, thickness, area, and lengths in 18 COPD patients at necropsy. We compared these results with data obtained from 22 non-COPD patients matched with regard to age, height, weight, and sex distribution. In the COPD patients, diaphragm muscle mass was 213 +/- SD 69 g, thickness was .320 +/- .055 cm, area was 647 +/- 160 cm2, coronal muscle length was 27.8 +/- 4.0 cm and sagittal muscle length was 15.8 +/- 2.8 cm. These values were within +/- 8 percent of the comparable values in the non-COPD patients, with no significant differences. There was no correlation between diaphragm length and lung volume in 13 COPD patients with TLC and ten with RV measurements. We conclude that over the range of lung volume encountered (TLC 135 +/- 28 percent predicted, RV 102 +/- 29 percent predicted TLC), there is no evidence for permanent shortening of the diaphragm.

An unusual site and cause of disabling inspiratory and expiratory airflow limitation mimicking fixed upper airway obstruction is reported in two patients with sarcoidosis who had stenosis of almost the entire lengths of both main bronchi. The observed flows were consistent with a cross sectional airway diameter of 3 mm. The lumen of the trachea and proximal airways was not compromised.

This study examined the hearts of 55 patients dying of chronic obstructive pulmonary disease, with and without cor pulmonale, quantitated histologically the degree of myocardial fibrosis in the left and right ventricle, and determined the relationship to associated disease states. Comparison has been made to a control group of 17 patients free of cardiopulmonary disease. Patients with associated and advanced ischemic heart disease, as proved by marked atherosclerosis and myocardial infarction, have significantly increased myocardial fibrosis throughout all layers of the left ventricular wall in comparison to control patients or patients with chronic obstructive pulmonary disease free of associated cardiac disease. Right ventricular fibrosis was not significantly increased; however, one case showed a marked degree of fibrosis related to myocardial infarction. Subdivision of patients with chronic obstructive pulmonary disease into groups with definite anatomic right ventricular hypertrophy, a clinical diagnosis of cor pulmonale, or with chronic hypoxemia failed to show any difference in the percentage of myocardial fibrosis of the ventricles among these groups. Increased fibrosis of the right or left ventricle in patients with chronic obstructive pulmonary disease, therefore, is not related to the degree of myocardial hypertrophy pathologically, the hypoxemic state, or clinical heart failure, but to ischemic heart disease with myocardial infarction.

Thirty-six patients with chronic obstructive pulmonary disease (COPD) were studied by pulsed Doppler echocardiography. In 32 of the 36 patients, adequate Doppler signals were obtained in the pulmonary arterial trunk and correlated with right cardiac hemodynamics. The studied group included 26 patients with mean pulmonary arterial pressure (MPAP) greater than 20 mm Hg at rest (group A, with pulmonary hypertension) and six patients with MPAP of 20 mm Hg or less (group B, without pulmonary hypertension). A control group (group C) consisted of 12 subjects with normal hemodynamic data and pulmonary function. Analysis of Doppler data included flow velocity curve pattern, presence of a negative presystolic velocity, right ventricular pre-ejection period (RVPEP) and ejection period (RVEP), time between onset and peak of pulmonary velocity (time to peak velocity, TPV) and derived ratios of TPV/RVPEP and TPV/RVEP. In patients with pulmonary hypertension, the Doppler flow velocity curve in the pulmonary trunk showed a rapid acceleration and an early deceleration. The mean value for TPV was 78 +/- 12 msec in group A, 115 +/- 11 msec in group B, and 127 +/- 10 msec in group C. In patients with COPD, significant correlations were observed between TPV and log10 MPAP (r = -0.77; SEE = 0.07) and between TPV and log10 total pulmonary resistances (r = -0.84; SEE = 0.05). Accordingly, pulsed Doppler echocardiography may be a useful tool to predict pulmonary hypertension due to chronic pulmonary disease.

One of the important modes of action of theophylline in asthma and chronic obstructive airway disease may be the inhibition of airway inflammation. This hypothesis is based on in vitro and in vivo studies demonstrating that theophylline at therapeutic concentrations has an inhibitory activity on airway inflammation induced by allergic and nonallergic stimuli. Indirect evidence suggests that airway inflammation is an important determinant in the long-term outcome of chronic obstructive airway disease. The effect of theophylline on the long-term evolution of chronic obstructive lung disease remains to be proven.

A 57-year-old man who died suddenly with severe bilateral mainstem bronchial collapse is described, and an alteration of the elastic tissue in the membranous portion of the bronchi is identified. The morphologic abnormalities, physiologic dynamics, and potential clinical consequences of such an alteration are discussed.

The presence or absence of left ventricular dysfunction in chronic obstructive pulmonary disease has been debated for decades. I have reviewed the following evidence pertaining to this topic: (1) left ventricular pathologic abnormalities; (2) the methods used to determine left ventricular performance; (3) specific abnormalities of left ventricular function as revealed by systolic time intervals, left ventricular end-diastolic pressure, ejection fraction, isovolumic indices, and left ventricular function curves; and (4) pertinent experimental data. The bulk of the evidence indicates that the clinical symtoms of left-sided failure are unreliable in those with obstructive disease of the airways and that the great majority of patients have normal left ventricular function, once other causes are excluded. A small group of patients have some abnormalities in left ventricular performance, but these have not been clinically significant. The ultimate importance of such abnormalities awaits future investigation.

The purpose of the present clinical research was to establish the major site of resistance and obstruction in patients with severe, symptomatic chronic obstructive pulmonary disease. We used a noninvasive technique by measuring airflow in a plethysmograph after patients breathed air and after breathing a mixture of 80 percent helium and 20 percent oxygen. In group 1 were 14 patients (mean age, 63 +/- 7 years [+/- 1 SD]) with bronchitis. The ratio of their forced expiratory volume in one second over the vital capacity (FEV1/VC) was 43 +/- 10 percent (mean +/- 1 SD), and their single-breath carbon monoxide diffusing capacity (Dsb) was normal (125 +/- 41 percent of the predicted value). In group 2 were 13 patients with emphysema (mean age, 60 +/- 10 years), whose FEV1/VC was 33 +/- 11 percent and Dsb was 55 +/- 14 percent of predicted. All patients had abnormally low increases in the maximum expiratory flow at midvital capacity after breathing the helium-oxygen mixture. The range in group 1 was -11 percent to +14 percent and in group 2 was -10 percent to +15 percent. Normal subjects in our laboratory show increases of at least +24 percent. This indicates that the limitation of airflow occurs primarily in the small (less than 2 mm in internal diameter) and not the large airways.

Autopsy findings and a morphometric study of the lungs were compared in 18 subjects receiving nocturnal oxygen and 15 receiving continuous oxygen in the National Heart, Lung, and Blood Institute Nocturnal Oxygen Therapy Trial (about half of those who died). The emphysema score, average interalveolar wall distance, central airway lesions, peripheral airway lesions, and the ratio of weights of left ventricle plus septum to right ventricle were similar in the two groups. The causes of death in the two groups were also similar. This evidence supports the hypothesis that the improved prognosis observed with continuous oxygen therapy nocturnal oxygen therapy in patients with severe chronic airflow obstruction and hypoxemia was due to treatment. There was a trend for there to be more interstitial fibrosis and type 2 alveolar epithelial cell hyperplasia in those treated with nocturnal oxygen; in the hands of one observer, the type 2 cell hyperplasia was significant.

This report questions several commonly used definitions and commonly accepted concepts. It suggest that the term, "chronic airflow obstructions," should replace the terms, "chronic obstructive pulmonary disease," "chronic obstructive lung disease," or "chronic airway obstruction," because it is flow that is obstructed. It is suggested the term, "chronic mucous hypersecretion," be used, rather than "chronic bronchitis," and that the latter be avoided. Chronic bronchitis should not be equated with narrowing of the airway and emphysema with loss of elastic recoil. Chronic bronchitis, emphysema, and lesions of the small airways probably occur together more frequently than chance will allow because of a common etiologic agent, tobacco smoke. Chronic mucous hypersecretion without other airway or parenchymal lesions seldom produces airflow obstruction and does not impair prognosis significantly. Central airways are important in chronic airflow obstruction. It is time that someone found out what is happening in subjects with abnormal results on tests of the function of small airways. The definition of "destruction" as it occurs in emphysema is deceptive, and loss of recoil and emphysema may be separate conditions. The dysfunction that occurs in emphysematous lungs is due mainly to associated airway lesions and may perhaps be due in part to the site and nature of emphysematous lesions (as opposed to loss of elastic recoil).

We studied, over a four-year period, two adolescents with alpha 1-antitrypsin (AAT) deficiency who subsequently died from complications of hepatic cirrhosis. Serial pulmonary function studies indicated mild obstructive lung disease involving peripheral airways in both patients. Postmortem histologic and pulmonary morphometric studies indicated mild diffuse airspace and bronchial gland enlargement, and slight dilation of small airways. This airspace enlargement may represent the early stage of lung disease in AAT-deficient subjects and suggests that pulmonary anatomic changes may occur long before the onset of clinically and pathologically significant emphysema.

Pulmonary encroachment by a large chronic pericardial effusion is reported in a woman with pericardiocentesis whom we recently treated. A restrictive pulmonary impairment is documented with pulmonary function data obtained before and after drainage of the effusion and the patient's dyspnea improved.

To confirm the safety of transthoracic needle biopsy of the lung (TNB) in the outpatient setting, we reviewed our experience with 106 such procedures over three years. We compared the operating characteristics and morbidity with the 65 similar procedures we were asked to perform on hospitalized patients during the same period. Outpatients did not differ from inpatients in mean age, sex, incidence of clinically apparent COPD, size and location of lesion, or number of needle passes. The operating characteristics of the biopsy were the same for the two groups. Pneumothorax occurred in 29 (27 percent) of 106 outpatient and 26 (40 percent) of 65 inpatient TNBs. Few pneumothoraces not present upon completion of biopsy developed during four hours of observation or later. The requirement for chest tube drainage was similar for both groups, 5.7 and 4.6 percent, respectively. With appropriate caution, TNB can be performed safely on an outpatient basis and the cost of an uncomplicated procedure reduced by 27 percent.