The impact of smoking on mechanical properties of the lungs in idiopathic pulmonary fibrosis and sarcoidosis.

Interstitial lung disease is characterized by interstitial inflammatory cell infiltration and fibrosis, a reduction in lung volumes, an increase in lung elastic recoil, and rapid shallow respirations. However, the alterations in lung volumes and elastic recoil as well as in breathing pattern are extremely variable, and the values are normal in a number of patients. In order to determine whether the effects of smoking could account for the variability in lung volumes and breathing pattern, we evaluated the elastic properties of the lung and the respiratory frequency at rest and during exercise in smokers and in nonsmokers with idiopathic pulmonary fibrosis (IPF) or with sarcoidosis. The volume-pressure curve in patients with IPF who smoked was positioned upwards and to the left when compared with that in nonsmokers. Conversely, the volume-pressure curve in patients with sarcoidosis who smoked was shifted downwards and to the right. In both conditions the respiratory rate while at rest and during exercise was greater in the group of patients who demonstrated the lower positioning of volume-pressure curves of the lungs (i.e., nonsmokers with IPF and smokers with sarcoidosis). We conclude that the impact of smoking may account, at least in part, for the variability in lung volume and volume-pressure characteristics of the lungs as well as the variability in respiratory rates in patients with interstitial lung disease.

Gas exchange at a given degree of volume restriction is different in sarcoidosis and idiopathic pulmonary fibrosis.

PURPOSE: It is likely that the relationship between lung volume changes and gas exchange in patients with idiopathic pulmonary fibrosis (IPF) and patients with sarcoidosis is different since the two conditions vary widely in histopathology and prognosis. Few studies, however, have examined this relationship. The goal of this investigation was to measure diffusing capacity and gas exchange in patients with IPF and sarcoidosis in whom the reduction of lung volume was equivalent. PATIENTS AND METHODS: In 21 patients with IPF and 20 patients with pulmonary sarcoidosis with comparable reductions in lung volume, the single breath diffusing capacity for carbon monoxide and gas exchange at rest and during exercise were compared. RESULTS: The relationship between lung volume and gas transfer differed in the two groups of patients. Resting and exercise gas exchange tended to be relatively normal and the diffusing capacity was higher in patients with sarcoidosis than in those with IPF. These differences could not be attributed to disparities in race, age, smoking habits, or the radiographic stage of sarcoidosis. CONCLUSION: The preservation of gas exchange in sarcoidosis as opposed to IPF, despite equivalent degrees of volume restriction, suggests that different pathophysiologic mechanism underlie the volume loss and gas exchange defects seen in these disorders. Furthermore, these findings suggest that diffusing capacity may not be a sensitive indicator of pulmonary pathology in sarcoidosis since lung volume can be altered independently of abnormalities in the diffusing capacity.

Quantification of cells recovered by bronchoalveolar lavage. Comparison of cytocentrifuge preparations with the filter method.

Controversy exists as to the appropriate methods to use in the processing of bronchoalveolar lavage (BAL) fluid for total cell numbers and cellular differential analysis. It has been shown that cell losses (primarily lymphocytes) occur by the most commonly employed methods. Therefore, we examined the total cell and differential counts obtained by several methods of cytocentrifuge preparation and by the filter preparation in 46 consecutive patients with interstitial lung disease and 29 healthy volunteers undergoing bronchoalveolar lavage. The retrieved lavage fluid was pooled, and an aliquot was used to determine the total cell count, cell viability, and the differential cell count by the filter and cytocentrifuge techniques. The remaining fluid was centrifuged (800 g for 10 min), and the cell pellet was resuspended in Hank's balanced salt solution without Ca2+ and Mg2+. An aliquot of these centrifuged and resuspended cells was used for repeat determination of the cell viability, total cell count, and cellular differential by cytocentrifuge technique. Autologous serum was added to another aliquot of these centrifuged and resuspended cells to arrive at a 10% protein solution, and the cellular differential obtained by cytocentrifuged preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Idiopathic pulmonary fibrosis. Abnormalities in bronchoalveolar lavage fluid phospholipids.

Bronchoalveolar lavage has been used to sample cells and proteins in the distal lung. One of the major secretory products of the alveolar type II epithelial cells, pulmonary surfactant, can be recovered by lavage. Abnormalities in alveolar type II cells are found in biopsies of patients with idiopathic pulmonary fibrosis (IPF), and abnormalities of pulmonary surfactant phospholipids have been reported after diffuse lung injury in animals and in humans. Therefore, we questioned if abnormalities in lavage phospholipids might also occur in IPF, a chronic inflammatory disease of the alveolar epithelium and interstitium, and, if present, would these abnormalities reflect histopathologic changes or predict responsiveness to therapy. Fifteen untreated patients with IPF, diagnosed by open lung biopsy, were studied and were found to have less than half the amount of bronchoalveolar lavage phospholipid as that recovered from healthy volunteers (p less than 0.05). In addition, patients with IPF had a lower proportion of phosphatidylglycerol and a higher proportion of phosphatidylinositol in the recovered phospholipids than did healthy volunteers (p less than 0.05). The severity of these alterations in phospholipid composition correlated with more advanced fibrotic histopathologic changes. Patients with less depression of total phospholipids in lavage improved with corticosteroid therapy, whereas the patients with more severely decreased total phospholipid recovered in lavage did not.

Idiopathic pulmonary fibrosis. Pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy.

Analysis of bronchoalveolar lavage cellular constituents has been recommended as a valuable method for the characterization of the inflammatory cellular population and for studying cellular interactions in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF). However, the clinical relevance of the enumeration of cells in bronchoalveolar lavage fluid (BALF) from patients with IPF remains controversial. We therefore examined the correlations between BALF cellular constituents and both the histopathologic abnormalities and the subsequent clinical response to corticosteroid therapy in 26 newly diagnosed, untreated patients with IPF. The BALF lymphocytosis was associated with moderate-to-severe alveolar septal inflammation (p less than 0.0005) and with a relative lack of histologic honeycombing (p less than 0.05). On the other hand, BALF neutrophil and eosinophil contents did not significantly correlate with any of eleven particular histopathologic abnormalities, and BALF neutrophil and lymphocyte contents did not correlate with the degree of clinical impairment (quantitated by a composite score based on dyspnea, radiographic abnormalities, and physiologic impairment) upon presentation. However, BALF eosinophil content correlated significantly with the severity of clinical impairment, higher eosinophil counts being associated with more severe initial clinical impairment (p less than 0.01). Neither pretreatment BALF neutrophil nor eosinophil content was related to the frequency or magnitude of subsequent clinical change in 20 patients evaluated before and after 1 yr of corticosteroid therapy. In contrast, pretreatment BALF lymphocytosis was associated with significant subsequent clinical improvement (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar lavage fluid neutrophils increase after corticosteroid therapy in smokers with idiopathic pulmonary fibrosis.

Patients with idiopathic pulmonary fibrosis (IPF) are often cigarette smokers and are often being treated with corticosteroids at the time of bronchoalveolar lavage. We addressed the question of whether or not the bronchoalveolar lavage fluid (BALF) neutrophil content of patients with IPF undergoes changes in smokers different from those in nonsmokers after institution of corticosteroids. Eighteen patients were studied (10 smokers and 8 nonsmokers). Fourteen patients (6 smokers and 8 nonsmokers) were treated orally with prednisone. The histologic assessment of alveolar inflammation and inflammatory small airways disease was no different in smokers than in nonsmokers. None of the smokers treated with prednisone had pathologic evidence of emphysema in addition to IPF. Five of 6 smokers showed an increase in BALF neutrophils after 3 months of prednisone (p less than 0.05), whereas the nonsmokers' BALF neutrophils decreased or remained unchanged. This increase in BALF neutrophils in smokers was not associated with concomitant or subsequent clinical deterioration but, in fact, with clinical improvement after 3 months of therapy. These data indicate that the combination of cigarette smoking and corticosteroid therapy influences the BALF neutrophil content in patients with IPF and suggest that interval changes in BALF neutrophil content may not reflect the status of the inflammatory process or structural derangements in the lungs of some patients with IPF.

A clinical, radiographic, and physiologic scoring system for the longitudinal assessment of patients with idiopathic pulmonary fibrosis.

In order to develop a reproducible, quantifiable means of assessment of the clinical status of patients with idiopathic pulmonary fibrosis (IPF), a composite clinical-radiographic-physiologic (CRP) scoring system was devised, using 7 variables: dyspnea, chest radiograph, spirometry, lung volume, diffusion capacity, resting alveolar-arterial PO2, and exercise O2 saturation. To assess this scoring system, we examined the relationships between CRP scores and histopathologic findings, including a cellular pathology score composed of abnormalities deemed to be potentially reversible, a fibrotic pathology score based on abnormalities felt to be essentially irreversible, and an index of overall pathologic derangement (total pathology score), derived from the sum of the cellular and fibrotic scores. The initial CRP determination at the time of open lung biopsy correlated significantly with the total pathology score (r = 0.61, p less than 0.001). The CRP score determined after 6 months of corticosteroid therapy showed a significant correlation with the fibrotic pathology score present on open lung biopsy (r = 0.76, p less than 0.001). The change in CRP after 6 months of corticosteroid therapy tended to reflect the cellular histopathologic component of the open lung biopsy (r = -0.43, p less than 0.10). Moreover, in none of these relationships did any individual component of the CRP score correlate better with the respective histopathologic index than did the CRP score itself. These data suggest that this CRP score is useful for the estimation of the severity of underlying pathologic derangement and for the longitudinal quantitative assessment of clinical impairment in patients with IPF.