Cancer and interstitial lung disease

PURPOSE OF REVIEW: This review assesses the contribution of various conditions that cause interstitial lung disease to the development of cancer. RECENT FINDINGS: Interstitial lung diseases for which the available evidence suggests an increased risk of lung cancer include idiopathic pulmonary fibrosis, systemic sclerosis, and certain forms of pneumoconioses. The pathogenesis of lung cancer remains unclear, and the available data on inflammation-induced pulmonary fibrosis as a risk factor for lung cancer are summarized. There is inadequate evidence for any conclusions about the risk of solid tumors and hematologic malignancies in patients with sarcoidosis, rheumatoid arthritis, and systemic lupus erythematosus. An increased incidence of lymphoma is detected in Sj?gren's syndrome. For patients with dermatomyositis and polymyositis, there is a well-documented association with a wide range of cancers. SUMMARY: Further studies are needed to clarify the cause(s) and the mechanisms that link various interstitial lung diseases and cancer.     

Cancer in interstitial pulmonary fibrosis and sarcoidosis

The occurrence of lung cancer in patients with diffuse interstitial pulmonary disease is well-known. The incidence, however, varies and ranges from 9.8 to 38%. The pathogenesis of lung cancer in pulmonary fibrosis is unclear, but genetic as well as environmental factors seem to be involved.     

Diffuse interstitial pulmonary fibrosis and bronchial cancer

Mortality due to lung cancer was 25% (7/28) in this study of patients with diffuse interstitial pulmonary fibrosis. Opacities on the chest x-ray suggestive of lung cancer were observed in 5 of the 7 cases. All 7 had squamous cell carcinoma. The percentage of smokers was significantly higher in patients with pulmonary fibrosis who developed lung cancer than in those with fibrosis who did not develop lung cancer (p = 0.016). These 7 cases of lung cancer with pulmonary fibrosis were compared with 174 cases of lung cancer without associated fibrosis. Peripheral localizations and lower lobe involvement were higher in cases of lung cancer with pulmonary fibrosis.     

阜阳地区呼吸系统疾病住院患者疾病构成及发病情况分析

目的分析阜阳地区呼吸系统疾病住院患者疾病构成及发病情况。方法收集2007—2012年安徽省阜阳市人民医院呼吸科住院病历资料9 012份,进行疾病分类统计和构成比分析,分析各年度各类疾病住院人数的变化。结果我院6年间呼吸系统疾病中以慢性阻塞性肺疾病、肺癌及肺炎为主,平均构成比分别为34.31%、23.44%及12.30%。慢性阻塞性肺疾病随年份有下降趋势,肺癌、肺结核、间质性肺疾病和肺栓塞随年份有上升趋势。慢性阻塞性肺疾病以老年患者为主,60~79岁为高发年龄段,发生率为40.25%;而支气管哮喘多发于年轻患者;肺癌高发于60~69岁年龄段,发生率为35.55%,但有年轻化趋势;呼吸系统疾病整体发病率以60~69岁为最高峰。结论慢性阻塞性肺疾病、肺癌、肺炎仍为阜阳地区主要呼吸系统疾病,肺癌发病率上升,有年轻化趋势,肺结核、间质性肺病及肺栓塞构成比提高。     

肺纤维化与肺癌相关性的研究进展

肺纤维化是各种肺间质性疾病的最终结果,与肺癌关系密切,二者互为危险因素,同时二者在发病机制上有许多相似之处。因此,对于肺纤维化与肺癌相关性的研究,不仅可以明确肺纤维化的病因,还可以指导靶向药物的研究,进而提高患者的生存时间。     

Cellular senescence in normal and premature lung aging

The incidence of chronic respiratory diseases (e.g., chronic obstructive pulmonary disease, COPD) and interstitial lung diseases (e.g., pneumonia and lung fibrosis) increases with age. In addition to immune senescence, the accumulation of senescent cells directly in lung tissue might play a critical role in the increased prevalence of these pulmonary diseases. In the last couple of years, detailed studies have identified the presence of senescent cells in the aging lung and in diseased lungs of patients with COPD and lung fibrosis. Cellular senescence has been shown for epithelial cells of bronchi and alveoli as well as mesenchymal and vascular cells. Known risk factors for pulmonary diseases (cigarette smoke, air pollutions, bacterial infections, etc.) were identified in experimental studies as being possible mediators in the development of cellular senescence. The present findings indicate the importance of cellular senescence in normal lung aging and in premature aging of the lung in patients with COPD, lung fibrosis, and probably other respiratory diseases.     

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.     

Pulmonary fibrosis associated with tracheobronchial aspiration. A study of the frequency of hiatal hernia and gastroesophageal reflux in interstitial pulmonary fibrosis of obscure etiology.

Tracheobronchial aspiration of gastric secretions has been suggested in published reports as a possible cause for idiopathic pulmonary fibrosis. Forty-eight of 131 patients with roentgenographic evidence of pulmonary fibrosis had no established etiologic diagnosis after individualized evaluations. They were prospectively studied by upper gastrointestinal series to determine the incidence of gastroesophageal reflux. The incidence of both hiatal hernia and reflux were statistically higher in the study group than in a group of 270 age-matched controls who had upper gastrointestinal series for the usual indications; (2) a subgroup of 15 patients who had pulmonary fibrosis and serologic evidence which suggested immune-mediated diseases; and (3) a subgroup of 23 patients with pulmonary fibrosis of established etiology. The patients in the study group could be further characterized by clinical and roentgenographic presentations, low maximum-mid-expiratory flow rates, and lung biopsies compatible with interstitial fibrosis. These observations and other cited evidence are supportive of the concept that repeated, small tracheobronchial aspirations of gastric acid secretions over a long period of time may cause interstitial pulmonary fibrosis.     

Bronchoalveolar lavage analysis with anti-T6 monoclonal antibody in the evaluation of diffuse lung diseases

To evaluate the usefulness of anti-T6 monoclonal antibody cell analysis in the assessment of diffuse lung disease, 77 bronchoalveolar lavages (BAL) were performed on 70 subjects: 18 normal smokers, 14 normal nonsmokers, 30 patients with chronic interstitial lung diseases (15 sarcoidosis, 12 idiopathic or associated pulmonary fibrosis, 3 histiocytosis X) and 8 patients with diffuse lung neoplastic disorders. The percentage of T6-positive cells was significantly higher in normal smokers than in normal nonsmokers (p less than 0.05). Positive T6 cells were absent or less than 1% in normal subjects, in patients with interstitial lung diseases and in patients with diffuse lung cancer, except in a case of desquamative interstitial pneumonitis, who had 2% of reacting cells. In contrast, such cells were always 3% or higher in the 6 BAL performed in histiocytosis X patients (p less than 0.05).     

Registration of interstitial lung diseases by 20 centres of respiratory medicine in Flanders

We report the results of a prospective registration of the prevalence of interstitial lung diseases by 20 centres of respiratory medicine in Flanders from January 1992 till July 1996. The 20 centres registered a total of 362 cases. Sarcoidosis (31% with inclusion of stage I, or 22% without stage I), idiopathic pulmonary fibrosis (20%), hypersensitivity pneumonitis (13%) and unclassified forms of interstitial lung diseases (9%) were the most often diagnosed diseases. The mean age of the patients was 52 +/- 17 (SD) years, but ranged from 32 +/- 10 years in histiocytosis X to 70 +/- 13 years in drug induced interstitial lung diseases. The male to female ratio was 1.3 but ranged from 2.3 in interstitial lung diseases due to inhalation of inorganic materials to 0.8 in interstitial lung diseases due to connective tissue disease. The diagnosis was considered certain in 60%, probable in 30% and possible in 10%. In 50% of the cases the diagnosis was proven by biopsy and the most often used biopsy technique was transbronchiolo-alveolar biopsy (40% of biopsies) followed by open lung biopsy (32%). At diagnosis vital capacity was 82 +/- 22% pred. (ranging from 92 +/- 19% in sarcoidosis to 71 +/- 24% in idiopathic pulmonary fibrosis) and CO-diffusing capacity was 77 +/- 19% pred. (ranging from 77 +/- 19% in sarcoidosis to 41 +/- 13% in drug induced pneumonitis). The regional frequency of interstitial lung diseases in Flanders varied widely and was not proportional to the regional distribution of the 20 contributing centres. In conclusion this registration provides interesting information on the occurrence and presentation of the different forms of interstitial lung diseases, although it may still underestimate the real prevalence and incidence of interstitial lung diseases.     

经支气管镜肺活检对弥漫性肺间质性疾病的诊断价值及文献复习

目的探讨经支气管镜肺活检（TBLB）对弥漫性肺间质性疾病（DILD）的诊断价值。方法对71例DILD患者在无X线电视透视下行TBLB,并对临床资料及病理诊断结果进行回顾性分析。结果 71例DILD中22例明确诊断,确诊率达31.0%,确诊的疾病种类主要有肺结核7例（31.8%）,普通型间质性肺炎5例（22.7%）,肺泡细胞癌4例（18.2%）,转移性肺癌2例（9.1%）,肺真菌病1例（4.5%）结节病1例（4.5%）,肺泡微石症1例（4.5%）,隐原性机化性肺炎1例（4.5%）;临床诊断病例共31例,诊断率达43.7%,其中特发性肺纤维化15例（48.4%）,结缔组织病相关肺疾病11例,弥漫性泛细支气管炎2例（6.5%）,癌性淋巴管炎2例（6.5%）,炎性假瘤1例（3.2%）;未能明确诊断18例（25.4%）。结论 TBLB对DILD的诊断是一种安全、简便、有效的方法,特别是在除外结节病、肿瘤和某些特殊类型的感染（结核）有重要价值。肺间质性疾病的病理诊断特别是病理分型需要较大的组织,必要时可行胸腔镜（VATS）肺活检或开胸肺活检,以提高对DILD的诊断水平。     

Gastro-oesophageal reflux and interstitial lung disease

BACKGROUND: Interstitial lung disease is a heterogeneous entity, which encompasses a large number of pulmonary disorders, including idiopathic pulmonary fibrosis. Gastro-oesophageal reflux appears to be more prevalent in idiopathic pulmonary fibrosis than in controls and in patients with secondary pulmonary fibrosis, but its contribution to interstitial lung disease remains unsettled. AIMS: To prospectively evaluate gastro-oesophageal reflux in patients with interstitial lung disease and to define acid reflux patterns in patients with idiopathic and secondary forms of pulmonary fibrosis. MATERIALS AND METHODS: Twenty-eight patients (15M, median age 66 years, interquartile range 60-71) were studied by history taking, pulmonary function tests, high resolution computed tomography, oesophageal manometry and 24h oesophago-gastric pH monitoring. RESULTS: Sixteen patients (57%) had typical reflux symptoms. All patients completed 24h pH metry and 14 underwent oesophageal manometry. An abnormal oesophageal acid exposure was observed in 19 patients (68%), 13 of which complained of predominant typical reflux symptoms. A diagnosis of idiopathic pulmonary fibrosis was made in 18 patients, while the remaining 10 patients were classified as secondary pulmonary fibrosis. Secondary pulmonary fibrosis patients had more restrictive lung defect, as expressed as Tiffeneau index (p<0.05) and greater acid reflux at nighttime (p<0.05) than idiopathic pulmonary fibrosis patients. CONCLUSIONS: The prevalence of abnormal acid reflux in interstitial lung disease patients is high and, in particular, patients with secondary pulmonary fibrosis show higher oesophageal acid exposure than those with idiopathic form.     

肺气肿合并肺间质纤维化的临床研究

目的　总结肺气肿合并肺间质纤维化的临床特点并探讨其临床意义。方法　分析５ 年来我院确诊的１１ 例肺气肿合并肺间质纤维化患者的症状、Ｘ线胸片、血气分析、肺功能、ＣＴ结果。结果　肺气肿合并肺间质纤维化患者多具有较长的吸烟史,临床表现介于上述两种病变之间,其肺功能测定结果不完全符合阻塞型或限制型通气功能障碍,Ｘ 线及ＣＴ兼具二者的特点。结论　尽管肺气肿和肺间质纤维化是两种不同的疾病,但是确实可以并存,且具有其独特的临床表现,胸部高分辨ＣＴ（ＨＲＣＴ）往往能为临床提供重要的诊断依据。     

Does interstitial lung disease predispose to lung cancer?

PURPOSE OF REVIEW: This review examines the evidence for the causality and pathogenesis of lung cancer associated with interstitial lung disease. RECENT FINDINGS: Although cigarette smoking is the leading cause of lung cancer, several other conditions either predispose to lung cancer or increase the risk of lung cancer in smokers. The evidence supports an increased risk of lung cancer due to specific fibrotic and inflammatory lung diseases (termed interstitial lung diseases), including idiopathic pulmonary fibrosis, systemic sclerosis, and certain pneumoconioses. The potential pathogenetic mechanisms indicate that recurrent injury and inflammation result in genetic alterations that predispose to lung cancer. SUMMARY: Idiopathic pulmonary fibrosis, systemic sclerosis, and certain pneumoconioses are associated with an independent increased risk of lung cancer; however, a unifying pathogenetic mechanism to explain the causality of this association has not been described. In addition, the inconsistently reported lung cancer frequencies call attention to the need for prospective studies of good quality.     

Algorithm for diagnosing pulmonary fibrosis in tropical countries

An algorithm for diagnosis of pulmonary fibrosis in the tropical countries has been developed on the basis of the common causes of fibrosis, and the availability and feasibility of different diagnostic techniques in those countries. First, it is important to exclude common diseases such as the atypical or occult forms of bronchiectasis, pulmonary tuberculosis, and chronic bronchitis, which often overshadow interstitial pulmonary fibrosis. A good history and physical examination supplemented with chest radiography and simple lung function tests are generally enough to narrow down the list of causes of diffuse lung disease to interstitial pulmonary fibrosis. The real difficulty lies in identifying the idiopathic or "lone" forms from the secondary forms of pulmonary fibrosis. High-resolution CT is helpful in a large number of patients. Transbronchial lung biopsy is performed in a select population of patients. Open surgical or thoracoscopy guided biopsy is the gold standard, but is rarely required.     

Rehabilitation and palliative care in lung fibrosis

The idiopathic interstitial pneumonias are a heterogeneous group of diffuse parenchymal lung diseases with varying degrees of inflammation and fibrosis, like interstitial pulmonary fibrosis. Functional exercise tolerance and quality of life have been shown to be significantly affected in patients with lung fibrosis. Moreover, interstitial pulmonary fibrosis is a progressive disease with poor prognosis and limited response to conventional pharmacological treatment like immunosuppressive agents. So, in patients with lung fibrosis there seems a clear indication to refer them for comprehensive pulmonary rehabilitation programmes and to initiate palliative care in an early phase of the disease. In the current review we will present a rationale for pulmonary rehabilitation in patients with lung fibrosis and the effects of this type of non-pharmacological intervention on exercise capacity and quality of life. In addition, we will discuss possibilities for palliative care in these patients.     

Smoking-related interstitial lung diseases: a concise review.

Interstitial lung diseases (also known as diffuse infiltrative lung diseases) are a heterogeneous group of parenchymal lung disorders of known or unknown cause. These disorders are usually associated with dyspnoea, diffuse lung infiltrates, and impaired gas exchange. The majority of interstitial lung diseases are of unknown cause. Known causes of interstitial lung disease include inhalation of organic and inorganic dusts as well as gases or fumes, drugs, radiation, and infections. This review summarizes the clinical, radiological, and histopathological features of four interstitial lung disorders that have been linked to smoking. These disorders include desquamative interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, pulmonary Langerhans' cell histiocytosis, and idiopathic pulmonary fibrosis. Available evidence suggests most cases of desquamative interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, and pulmonary Langerhans' cell histiocytosis are caused by cigarette smoking in susceptible individuals. Smoking cessation should be a main component in the initial therapeutic approach to smokers with these interstitial lung diseases. In addition, smoking appears to be a risk factor for the development of idiopathic pulmonary fibrosis.     

Surgical biopsy: its appropriateness in diagnosing interstitial lung disease

PURPOSE OF REVIEW: Our goal is to update advances in the use of surgical lung biopsy in the idiopathic interstitial pneumonias. We discuss an approach for identifying patients with idiopathic interstitial pneumonias who may benefit from surgical lung biopsy, newer surgical approaches and complications and risks of surgery. RECENT FINDINGS: A consensus statement on idiopathic interstitial pneumonias has described the natural history and response to therapy of idiopathic interstitial pneumonias. The statement discussed selection of patients with idiopathic interstitial pneumonias for surgical lung biopsy and avoidance of unneeded biopsy, particularly for patients with 'classical' radiographic findings of idiopathic pulmonary fibrosis. Video-assisted thoracoscopic lung biopsy continues to be the standard procedure for surgical lung biopsy. Newer approaches have used outpatient surgery for selected patients, earlier removal of chest tubes and modifications of surgical technique. At-risk patients include those with respiratory failure, rapid progression of disease, pulmonary hypertension and advanced disease. SUMMARY: Standard video-assisted thoracoscopic lung biopsy should be considered in patients with interstitial lung diseases of unknown cause who have a subacute course, ground-glass opacities on high-resolution computed tomography or features atypical for idiopathic pulmonary fibrosis, as these patients may respond to therapy. A step-wise process for selection of patients for surgical lung biopsy is recommended.     

Lack of evidence for a role of Epstein-Barr virus in the increase of lung cancer in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is known as an independent risk factor for lung cancer. Because Epstein-Barr virus (EBV) may be involved in the genesis of IPF as well as certain malignancies, we investigated whether EBV contributes to the increased incidence of lung cancer in IPF The formalin-fixed and paraffin-embedded lung sections were prepared from 22 lung cancer patients with IPF and 22 lung cancer patients without IPF All ofthe IPF patients pathologically showed usual interstitial pneumonia. In situ hybridization for EBV-encoded small non-polyadenylated RNAs failed to show positive signals in the cancer tissues of either IPF or non-IPF patients. This study did not provide evidence for an etiologic role of EBV in the development of lung cancer in IPF.     

间质性肺疾病与肺癌

间质性肺疾病(ILD)患者中肺癌的发病率增高,特别是特发性肺纤维化合并肺癌的报道最多.ILD合并肺癌的病理类型以鳞状细胞癌最多,好发于肺下叶和外周部位.ILD的一些肿瘤标记物增高,与疾病的活动程度、严重程度、肺纤维化程度和病情预后等有关,并且具有一定的诊断价值.ILD的肿瘤标记物增高可能是其合并肺癌的危险因素.本文对I...