Smoking-related Interstitial Fibrosis Research Articles

Smoking-Related Interstitial Fibrosis and Smoker's Macrophages.

Smoking-related interstitial lung diseases (SRILDs) are a group of heterogeneous diffuse pulmonary parenchymal diseases associated with tobacco exposure. Smoking-related interstitial fibrosis (SRIF) is relatively recent, a pathologically defined form of SRILDs. SRIF is characterized by the accumulation of macrophages in the alveolar spaces, which is associated with interstitial inflammation and fibrosis. The macrophages frequently contain light brown pigment and are called 'smoker's macrophages'. Patients with SRIF who have clinical evidence of interstitial lung disease are most commonly relatively young, heavy smokers with abnormalities on chest computed tomography showing ground-glass opacities, peripheral consolidation, and reticulation. Although SRIF is caused by cigarette smoking, the exact pathophysiological mechanisms by which smoking causes this type of interstitial fibrosis remain unknown. The degree of fibrosis and appearance of macrophage aggregates are important points of distinction when evaluating and diagnosing SRIF. Macrophage heterogeneity, particularly the activation and function of monocyte-derived alveolar macrophages (Mo-AMs) and interstitial macrophages (IMs), has important implications for the pathogenesis of SRIF and developing treatments. Further researches focused on smoker's macrophages are needed to understand of the pathogenesis of SRIF.

Smoking-Related Interstitial Fibrosis (SRIF) in Patients Presenting With Diffuse Parenchymal Lung Disease

To describe the clinical, radiologic, and pathologic findings in cases where smoking-related interstitial fibrosis (SRIF) was diagnosed in surgical lung biopsy specimens from patients with clinical and imaging features of diffuse parenchymal lung disease (DPLD). Cases were included in this study if patients had clinical and imaging evidence of DPLD and surgical lung biopsy specimens revealed SRIF. A dedicated multidisciplinary conference was held to correlate clinical, radiologic, and pathologic findings. Six cases met inclusion criteria; all six (five women/one man, aged 42-57 years, mean age 47 years) were either current smokers (five of six) or ex-smokers (one of six) and were evaluated for respiratory symptoms and abnormal pulmonary function tests, most commonly reduced forced vital capacity (n = 3) and diffusing capacity for carbon monoxide (n = 6). The most common imaging abnormalities were bilateral ground-glass opacities, which correlated with histopathologic SRIF. Follow-up of up to 10 years showed stable or improved clinical symptoms, pulmonary function tests, and radiologic findings with smoking cessation (three patients) or a decrease in smoking (three patients). No specific treatments were given, and those treated with empiric corticosteroid tapers did not show discernible responses. SRIF can present as clinically meaningful diffuse parenchymal lung disease in relatively young heavy smokers, characterized by bilateral ground-glass opacities and a stable clinical course.

Smoking-related interstitial lung disease

Exposure to smoke is associated with the development of diseases of the airways and lung parenchyma. Apart from chronic obstructive pulmonary disease (COPD), in some individuals, tobacco smoke can also trigger mechanisms of interstitial damage that result in various pathological changes and pulmonary fibrosis. A causal relation has been established between tobacco smoke and a group of entities that includes respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP), Langerhans cell histiocytosis (LCH), and acute eosinophilic pneumonia (AEP). Smoking is considered a risk factor for idiopathic pulmonary fibrosis (IPF); however, the role and impact of smoking in the development of this differentiated clinical entity, which has also been called combined pulmonary fibrosis and emphysema (CPFE) as well as nonspecific interstitial pneumonia (NIP), remains to be determined. The definition of smoking-related interstitial fibrosis (SRIF) is relatively recent, with differentiated histological characteristics. The likely interconnection between the mechanisms involved in inflammation and pulmonary fibrosis in all these processes often results in an overlapping of clinical, radiological, and histological features in the same patient that can sometimes lead to radiological patterns of interstitial lung disease that are impossible to classify. For this reason, a combined approach to diagnosis is recommendable. This combined approach should be based on the joint interpretation of the histological and radiological findings while taking the clinical context into consideration. This paper aims to describe the high-resolution computed tomography (HRCT) findings in this group of disease entities in correlation with the clinical manifestations and histological changes underlying the radiological pattern.

Enfermedades pulmonares intersticiales relacionadas con el tabaco

Exposure to smoke is associated with the development of diseases of the airways and lung parenchyma. Apart from chronic obstructive pulmonary disease (COPD), in some individuals, tobacco smoke can also trigger mechanisms of interstitial damage that result in various pathological changes and pulmonary fibrosis. A causal relation has been established between tobacco smoke and a group of entities that includes respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP), Langerhans cell histiocytosis (LCH), and acute eosinophilic pneumonia (AEP). Smoking is considered a risk factor for idiopathic pulmonary fibrosis (IPF); however, the role and impact of smoking in the development of this differentiated clinical entity, which has also been called combined pulmonary fibrosis and emphysema (CPFE) as well as nonspecific interstitial pneumonia (NIP), remains to be determined. The definition of smoking-related interstitial fibrosis (SRIF) is relatively recent, with differentiated histological characteristics. The likely interconnection between the mechanisms involved in inflammation and pulmonary fibrosis in all these processes often results in an overlapping of clinical, radiological, and histological features in the same patient that can sometimes lead to radiological patterns of interstitial lung disease that are impossible to classify. For this reason, a combined approach to diagnosis is recommendable. This combined approach should be based on the joint interpretation of the histological and radiological findings while taking the clinical context into consideration. This paper aims to describe the high-resolution computed tomography (HRCT) findings in this group of disease entities in correlation with the clinical manifestations and histological changes underlying the radiological pattern.

Smoke-related interstitial fibrosis – a case report

Smoking-related interstitial fibrosis (SRIF) is a recently described disease which is common finding in a long-term cigarette smokers.Aim. To acquaint readers with relatively unknown interstitial disease. We describe a case of a smoking patient with a long smoking history and squamous cell carcinomas of the larynx and lung who complained of an unproductive cough, sore throat, hoarseness, difficulty in nasal breathing, and shortness of breath during exercise. Obstructive disorders, lung hyperinflation, and a severe decrease in diffusion capacity reflected the signs of severe emphysema in combination with fibrotic changes found by high resolution computed tomography (CT). X-ray picture and characteristic histological changes made it possible to diagnose SRIF.Conclusion. Diagnostics of the disease should be based on CT-signs, histologic picture and functional data. The prognosis is relatively favorable.

Syndrome of Combined Pulmonary Fibrosis and Emphysema: An Official ATS/ERS/JRS/ALAT Research Statement.

Background: The presence of emphysema is relatively common in patients with fibrotic interstitial lung disease. This has been designated combined pulmonary fibrosis and emphysema (CPFE). The lack of consensus over definitions and diagnostic criteria has limited CPFE research. Goals: The objectives of this task force were to review the terminology, definition, characteristics, pathophysiology, and research priorities of CPFE and to explore whether CPFE is a syndrome. Methods: This research statement was developed by a committee including 19 pulmonologists, 5 radiologists, 3 pathologists, 2 methodologists, and 2 patient representatives. The final document was supported by a focused systematic review that identified and summarized all recent publications related to CPFE. Results: This task force identified that patients with CPFE are predominantly male, with a history of smoking, severe dyspnea, relatively preserved airflow rates and lung volumes on spirometry, severely impaired DlCO, exertional hypoxemia, frequent pulmonary hypertension, and a dismal prognosis. The committee proposes to identify CPFE as a syndrome, given the clustering of pulmonary fibrosis and emphysema, shared pathogenetic pathways, unique considerations related to disease progression, increased risk of complications (pulmonary hypertension, lung cancer, and/or mortality), and implications for clinical trial design. There are varying features of interstitial lung disease and emphysema in CPFE. The committee offers a research definition and classification criteria and proposes that studies on CPFE include a comprehensive description of radiologic and, when available, pathological patterns, including some recently described patterns such as smoking-related interstitial fibrosis. Conclusions: This statement delineates the syndrome of CPFE and highlights research priorities.

Pathological and clinical relevance of selective recruitment of Langerhans cells in the respiratory bronchioles of smokers

Smoking causes an influx of inflammatory cells including Langerhans cells (LCs) into the airways and lung parenchyma, thus inducing histological changes, such as emphysema and fibrosis. We examined the distribution and quantity of Langerhans cells in relation to clinical and pathological findings and explored the association between smoking and accumulation of Langerhans cells in the respiratory bronchioles. Fifty-three patients who underwent lung resection for primary diseases, including lung cancer, were recruited. Histological and immunohistochemistry analyses were utilized to identify CD1a-positive Langerhans cells in peripheral lung specimens separated from primary lesions. Clinical characteristics, pathological changes, and distribution of CD1a-positive Langerhans cells distribution were assessed. Of the 53 patients, 35 were smokers and 18 were non-smokers. The number of Langerhans cells in the respiratory bronchioles was significantly increased in smokers as compared to that in non-smokers (p<0.001). The number of Langerhans cells in smokers was significantly higher in patients with mild emphysema than in those without emphysema (p<0.01). The high-LC group showed more frequent smoking-related histological changes, such as respiratory bronchiolitis, parenchymal fibrosis, accumulation of macrophages, and smoking-related interstitial fibrosis, than the low-LC group. However, there were no differences in the smoking indices and pulmonary functions of the groups. Selective accumulation of Langerhans cells in the respiratory bronchioles of smokers may lead to the development of smoking-related pathological changes.

To pay attention to smoking-related interstitial fibrosis

吸烟相关性肺间质纤维化（SRIF）是病理学家近来在吸烟者肺组织中发现并命名的一种疾病，属于吸烟相关性间质性肺疾病（SRILD）范畴，其具有特征性的粗大、绳索样、玻璃样变的胶原沉积于显著增宽的肺泡间隔内。SRIF预后很好，但在病理组织学及影像学上，其与普通性间质性肺炎及其他预后差的间质性肺炎有相似之处，故需要进行鉴别。

Computer-aided Quantification of Pulmonary Fibrosis in Patients with Lung Cancer: Relationship to Disease-free Survival.

Background Interstitial lung abnormalities (ILAs) are present at CT in about 10% of individuals undergoing lung cancer screening. The relationship between histologic findings of ILAs and their influence on patient prognosis remains unknown. Purpose To evaluate the percentage of ILAs at preoperative CT, as measured by radiologists and a computer-aided detection (CAD) software, as a predictor of disease-free survival in patients with lung cancer. Materials and Methods This retrospective study evaluated 217 consecutive patients who underwent complete resection of lung cancer from April 2010 to December 2015. Two radiologists, blinded to the patients' clinical information, scored percentage fibrosis extent and determined whether ILAs and the usual interstitial pneumonia (UIP) pattern were present. They assessed ILA progression at follow-up CT. Two pathologists determined the presence of an UIP pattern. Percentage fibrosis extent was also measured by using CAD. Binary logistic regression analysis was performed to determine whether the CAD percentage fibrosis extent was associated with ILA at CT. Multivariable Cox regression analysis was used to evaluate the significance of CAD percentage fibrosis extent as a predictor of prognosis. Results The radiologists classified 47 patients with ILAs and 24 patients with a UIP pattern at chest CT. The pathologists detected a UIP pattern in 25 patients. CT abnormalities showed progression over a 2-year period in all patients with histologic evidence of UIP. After adjustment for age, sex, and smoking index, the CAD percentage fibrosis extent was independently associated with ILA (odds ratio: 3.1; 95% confidence interval [CI]: 2.1, 4.7; P < .001). After adjustment for age, forced expiratory volume in 1 second (percentage predicted) radiologist-assessed percentage fibrosis extent, and pathologic stage, CAD percentage fibrosis extent was independently associated with worse disease-free survival (hazard ratio: 1.3; 95% CI: 1.1, 1.6; P < .001). Conclusion Greater computer-aided detection percentage fibrosis extent at preoperative CT independently predicted worse disease-free survival in patients with lung cancer. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Goo in this issue.

A Review of Smoking-Related Interstitial Fibrosis, Respiratory Bronchiolitis, and Desquamative Interstitial Pneumonia: Overlapping Histology and Confusing Terminology.

Smoking-related lung diseases traverse a spectrum of clinicopathologic entities, with cases often comprising a complex mixture of findings. The complexity of the diagnostic process extends beyond the histologic findings to the nomenclature, which is murky from a seemingly unending expansion of terms being applied to a handful of pathologic changes. Here, we focus our review on smoking-related interstitial fibrosis, respiratory bronchiolitis, and desquamative interstitial pneumonia, 3 entities that perhaps show the most histologic overlap and suffer from competing terminology.

Pathologic features of smoking-related lung diseases, with emphasis on smoking-related interstitial fibrosis and a consideration of differential diagnoses.

Smoking-related interstitial fibrosis (SRIF) is frequently-seen and morphologically-distinctive finding in the lung tissue of cigarette smokers. It can be distinguished histologically from the idiopathic interstitial pneumonias and other causes of pulmonary interstitial fibrosis. SRIF is typified by dense thickening of the alveolar septa by thick collagen bundles with a hyalinized appearance, with the common admixture of bands of hyperplastic smooth muscle. Concomitant inflammation is minimal. SRIF predominates in the subpleural and centrilobular parenchyma, and is usually accompanied by the changes of centrilobular emphysema and respiratory bronchiolitis. Most patients with SRIF do not have clinical symptoms of the condition. This article reviews the pathologic features of SRIF and compares them with the appearances of other interstitial lung diseases, some of which are also related to cigarette smoking. Acute eosinophilic pneumonia is another lung disease that has an association with smoking, and its clinicopathologic features are considered here as well.

Pulmonary cysts in smoking-related interstitial fibrosis: a form of pseudocyst secondary to pulmonary interstitial emphysema

Smoking-related interstitial fibrosis is a distinct form of fibrosis, found in smokers, which has striking histopathological features. We present a case of pulmonary interstitial fibrosis with cysts in a 58-year-old woman who was a significant active smoker, presenting with a 7 month history of progressive dyspnea. TAC revealed thin-walled pulmonary cysts. An open lung biopsy was performed and the histopathological study showed hyaline fibrous thickening of the alveolar septa, respiratory bronchiolitis and cysts in the thickness of the interlobar septa. Immunohistochemically, the absence of an epithelial, vascular or lymphatic endothelial lining of the cysts would suggest that the cysts had been caused by pulmonary interstitial emphysema. Immunohistochemistry is essential in the differential diagnosis that includes, in this case, true cysts, pseudocysts and pulmonary lymphangiectasia.

Smoking-Related Interstitial Fibrosis: Evidence of Radiologic Regression with Advancing Age and Smoking Cessation

ABSTRACTMore data are needed regarding the radiology, co-morbidities and natural history of smoking-related interstitial fibrosis (SRIF), a common pathological finding, mainly described heretofore in association with lung cancer, where respiratory bronchiolitis (RB) usually co-exists.We prospectively acquired high resolution CT scan data (edge-enhancing lung reconstructions) to detect any radiologic interstitial lung abnormality (ILA) in individuals who ultimately underwent surgical lobectomy for lung cancer (n = 20), for radiologic/pathologic correlation. We also re-examined other smoking-related benign histologic cases: chronic obstructive pulmonary disease (COPD lung explants, n = 20), alpha 1-antitrypsin deficiency (A1AT, explanted lungs n = 20), combined pulmonary fibrosis and emphysema (CPFE, n = 8) and idiopathic pulmonary fibrosis (IPF, n = 10). Finally, we pooled our data with all peer-reviewed published data describing histologic SRIF of known ILA status.SRIF was observed in 40% of cancer lobectomies, mean (±SD) age 65.8 ± 8.7 years, none of whom had ILA. SRIF was observed in other smoking-related benign diseases (COPD 35%, A1AT 20%, CPFE 25%, and IPF 10%). 71.4% of benign SRIF cases had no RB (nearly all ex-smokers) versus 0% of cancer-associated SRIF cases (P = 1.7 × 10−3). Pooled data showed that those SRIF subjects without ILA were 15.05 years older than those with ILA (95% confidence interval 8.99 to 21.11, P = 2.5 × 10−5) and more likely to be former smokers (P = 7.2 × 10−3).SRIF is frequently found without lung cancer, and mostly without RB in former smokers. SRIF is less likely to have ILA in older subjects and with smoking cessation, which could represent RB+/−SRIF regression.

Differentiating Smoking-Related Interstitial Fibrosis (SRIF) from Usual Interstitial Pneumonia (UIP) with Emphysema Using CT Features Based on Pathologically Proven Cases.

ObjectiveTo differentiate smoking-related interstitial fibrosis (SRIF) from usual interstitial pneumonia (UIP) with emphysema on CT in combined pulmonary fibrosis and emphysema (CPFE) patients.Materials and MethodsThis study was approved by the institutional review board and informed consent was waived. We included 65 patients who underwent lung biopsy under the suspicion of UIP pattern on HRCT, and after radiologic-pathologic correlation, they were divided into three groups: UIP without emphysema (n = 30), UIP with emphysema (n = 26), and SRIF (n = 9). The quantitative extent of emphysema in the entire lung was visually assessed and fibrotic patterns were qualitatively analyzed based on six characteristics (asymmetry, juxta-subpleural sparing, emphysema beside the honeycombing area, absence of ground grass attenuation/reticulation in honeycombing area, inhomogeneous honeycombing, and absence of honeycombing in the upper lobes). Kaplan-Meier analysis was used for survival analysis, and logistic regression with a receiver operating characteristic curve was used to predict the possibility of SRIF.ResultsIn qualitative analysis of fibrotic patterns, SRIF tended to exhibit more than three of six fibrotic features, whereas UIP with emphysema demonstrated about two of these characteristics (p = 0.035). In addition, SRIF had a higher extent of emphysema than UIP with emphysema when they have same amount of fibrosis (p = 0.014). In patients with SRIF, 5-year survival rate was 85.7%, while it was 40.7% in UIP with emphysema patients (p = 0.035).ConclusionFibrotic CT patterns and survival rate differed between SRIF and UIP with emphysema among CPFE patients, which explains the variable prognosis of CPFE.

One-year Follow-up of Three Cases of Smoking-related Interstitial Fibrosis

흡연연관 간질성 섬유증(SRIF)은 콜라젠 침착으로 인한 폐포 중격의 비후가 있고, 호흡세기관지염과 폐기종이 동반되어 있다는 것이 특징이다. 2010년도에 처음으로 SRIF 용어를 사용하기 시작하였으며, 임상, 조직, 영상 소견이 특발성폐섬유증과 구별되는 병리 소견이다. SRIF는 현재까지 국내에서 보고된 적 없으며, 세계적으로도 보고가 드물다. 저자들은 SRIF 3예를 1년간 추적 관찰하여 보고하는 바이다.

Smoking-related idiopathic interstitial pneumonia: A review.

For many years, cigarette smoking has been considered as the leading cause of chronic obstructive pulmonary disease and lung cancer. Recently, however, it has also been associated with the development of diffuse interstitial lung diseases. In the latest classification of the major idiopathic interstitial pneumonias (IIP), the term smoking-related IIP has been introduced, including two entities, namely desquamative interstitial pneumonia (DIP) and respiratory bronchiolitis-interstitial lung disease (RB-ILD). Other entities in which smoking has a definite or suggested role include pulmonary Langerhan's cell histiocytosis, smoking-related interstitial fibrosis, combined pulmonary fibrosis and emphysema syndrome and idiopathic pulmonary fibrosis. In this review, we will focus on the mechanisms of smoking-related lung damage and on the clinical aspects of these disorders with the exception of idiopathic pulmonary fibrosis, which will be reviewed elsewhere in this review series.

Interstitial lung disease related to smoking: imaging considerations.

To discuss the imaging of interstitial lung disease believed to be caused by smoking. It is increasingly clear that smoking is associated with a variety of patterns of interstitial lung disease. The radiologic features of interstitial lung disease caused by smoking cigarettes are variable and may be nonspecific. It is now accepted that cigarette smoking can cause lung diseases other than lung cancer, chronic bronchitis and emphysema. Indeed, the hypothesis that tobacco smoke can cause interstitial lung disease - and, specifically, pulmonary fibrosis - dates back to the 1960s. The list of interstitial lung disease, in which smoking is believed to have an etiologic role, includes Langerhans' cell histiocytosis, respiratory bronchiolitis/respiratory bronchiolitis-interstitial lung disease and desquamative interstitial pneumonia. More recently, there is emerging evidence which suggests that smoking may be associated with other patterns of pulmonary fibrosis (e.g. nonspecific interstitial pneumonia and smoking-related interstitial fibrosis). In the present review we discuss the imaging of the interstitial lung disease known to be caused by smoking; the typical appearances and some of the diagnostic difficulties are discussed.

Usual interstitial pneumonia and smoking-related interstitial fibrosis display epithelial to mesenchymal transition in fibroblastic foci

Fibroblastic foci (FF) are a major histological feature of usual interstitial pneumonia (UIP) in idiopathic pulmonary fibrosis (IPF) and collagen vascular diseases (non-IPF). In addition, FF are occasionally associated with smoking-related interstitial fibrosis (SRIF). Recent studies have suggested a role for epithelial to mesenchymal transition (EMT) in pulmonary fibrogenesis. Here, we investigated whether EMT was present in patients with IPF (n=19), non-IPF (n=17), and SRIF (n=16) using morphometric immunohistochemistry, electron microscopy, and confocal microscopy. All patients had received lung biopsies or lobectomies for lung cancer. IPF and non-IPF patients displayed restrictive lung function patterns, whereas those with SRIF presented mixed patterns. Cells within FF presented high number of alpha-smooth muscle actin (αSMA)-staining cells; however, the foci of IPF patients showed comparatively lower number. Moreover, colocalization of thyroid transcription factor-1 (TTF1) and αSMA within FF showed low number of staining cells for IPF and SRIF in comparison to non-IPF (p<0.01). Nevertheless, all groups displayed colocalization of high rate of TTF1(+)-cells and low rate of αSMA(+)-cells within hyperplastic epithelioid cells in FF. Also, we observed areas with low proportion of TTF1(+)cells and αSMA(+)cells, which were present in SRIF and non-IPF more often than IPF (p<0.001). Electron microscopy revealed small breaks in the alveolar basal lamina, which allowed epithelioid cells to directly contact the collagenous matrix and fibroblasts. Three-dimensional reconstruction revealed intense αSMA staining within some epithelioid cells, suggesting that they had gained a mesenchymal phenotype. These findings constitute the first report of EMT in SRIF and suggest that EMT occurs more prominently in SRIF and non-IPF than IPF.

Pulmonary adenocarcinoma mutation profile in smokers with smoking-related interstitial fibrosis.

Cigarette smoking is an established cause of lung cancer. However, pulmonary fibrosis is also an independent risk factor for the development of lung cancer. Smoking-related interstitial fibrosis (SRIF) has recently been reported. We hypothesized that adenocarcinomas in lungs with SRIF might show distinct molecular changes and examined the molecular phenotype of 168 resected lung adenocarcinomas in lungs with and without SRIF. The diagnosis of SRIF was determined by histological examination, based on the presence of alveolar septal thickening, due to pauci-inflamed, hyalinized, “ropy” collagen, in areas of lung greater than 1 cm away from the tumor. Tumors were concomitantly examined genotypically for mutations in genes frequently altered in cancer, including EGFR and KRAS, by SNaPshot and by fluorescence in situ hybridization for possible ALK rearrangements. Fluorescence in situ hybridization for ROS1 rearrangement (n=36) and/or MET amplification (n=31) were performed when no mutation was identified by either SNaPshot or ALK analysis. Sixty-five cases (38.7%) showed SRIF, which was distributed in all lobes of the lungs examined. No differences were observed in sex, average age, or smoking history in patients with and without SRIF. There was no difference in either the percent or types of adenocarcinoma genetic mutations in patients with SRIF versus those without. This data suggests that SRIF does not represent an independent risk factor for the development of the major known and targeted mutations seen in pulmonary adenocarcinoma. However, additional research is required to investigate the potential significance of SRIF in the pathogenesis of lung cancer.

Respiratory bronchiolitis with fibrosis: a form of smoking-related disease

A new smoking-associated lesion has been described in the pathology literature over the last few years by various names including RBILD with fibrosis, smoking-related interstitial fibrosis, and airspace enlargement with fibrosis. The lesion consists of localized patches of paucicelluar interstitial fibrosis mixed with emphysema, and frequently forms a wedge shape under the pleura. We recently proposed that this lesion be called respiratory bronchiolitis with fibrosis (RBF) and showed that in at least some cases RBF has a distinctive high resolution CT (HRCT) appearance consisting of sharply circumscribed patches of subpleural reticulation mixed with emphysema. In an HRCT survey of heavy smokers we found this lesion in 5% of patients; but it is much more frequent in pathology specimens from heavy smokers. RBF, like smokers respiratory bronchiolitis, generally produces no symptoms and no demonstrable physiologic impairment, but in a fashion analogous to RBILD, a small fraction of patients have evidence of a mild interstitial lung disease which we suggest be called RBF-ILD. This lesion is often mistaken pathologically and radiologically for a diffuse fibrosing interstitial lung disease, but RBF-ILD is nonprogressive and does not evolve into a more serious form of interstitial lung disease.