Private specificities can dominate the humoral response to self-antigens in patients with cryptogenic fibrosing alveolitis

Background  

The pathogenetic mechanisms that underlie the interstitial lung disease cryptogenic fibrosing alveolitis (CFA) may involve an immunological reaction to unidentified antigens in the lung, resulting in tissue damage.     

Rising mortality from cryptogenic fibrosing alveolitis.

OBJECTIVE--To determine the pattern of mortality ascribed to cryptogenic fibrosing alveolitis and to identify factors that might be important in the aetiology of the disease; and to assess the validity of death certification of the disease. DESIGN--A retrospective examination of mortality ascribed to cryptogenic fibrosing alveolitis in England and Wales between 1979 and 1988 with analysis, by multiple logistic regression, of independent effects of age, sex, region of residence, and social class as indicated by occupation on data for 1979-87; also a retrospective review of hospital records of patients certified as having died of cryptogenic fibrosing alveolitis in Nottingham and of the certified cause of death of patients known to have had the disease. MAIN OUTCOME MEASURES--Time trends in mortality nationally; effects on mortality of age, sex, and region of residence; validity of death certification in Nottingham. RESULTS--The annual number of deaths ascribed to cryptogenic fibrosing alveolitis doubled from 336 in 1979 to 702 in 1988, the increase occurring mainly at ages over 65. Mortality standardised for age for both sexes likewise increased steadily over the period. Deaths due to cryptogenic fibrosing alveolitis were commoner in men (odds ratio 2.24, 95% confidence interval 2.11 to 2.33) and increased substantially with age, being 7.84 (7.24 to 8.49) times higher in subjects aged much greater than 75 than those aged 45-64. Odds ratios of death due to cryptogenic fibrosing alveolitis adjusted for age and sex were increased in the traditionally industrialised central areas of England and Wales (p less than 0.02, maximum odds ratio between regions 1.25), but no significant increase in odds of death was found for manual occupations. Of 23 people whose deaths were registered in Nottingham as having been due to cryptogenic fibrosing alveolitis, 19 were ascertained from clinical records to have had the disease. Only 17 of 45 patients known to have had cryptogenic fibrosing alveolitis in life were recorded as having died from the disease. CONCLUSIONS--The diagnostic accuracy of death certification of cryptogenic fibrosing alveolitis is high, but the number of deaths recorded as being due to the disease may underestimate the number of patients dying with the disease by up to half. Mortality due to the disease is increasing, and the male predominance and regional differences in mortality suggest that environmental factors are important in its aetiology.     

Lung Function in Patients Receiving Busulphan

An attempt was made to achieve earlier detection of busulphan lung (fibrosing alveolitis) and to determine its incidence by means of serial studies during life, including measurement of the gas transfer factor. Twenty-three patients were investigated over an average period of nearly two years of busulphan treatment. One case of busulphan lung was detected and subsequently confirmed at necropsy, but in the remainder there was no clinical, radiological, or physiological evidence of fibrosing alveolitis. It is concluded that the development of fibrosing alveolitis may be related to individual genetic or immunological factors rather than to busulphan dosage.     

TGF-beta1 在不同类型特发性间质性肺炎患者肺组织中的表达及其意义

目的:探讨TGF-β1在不同类型特发性间质性肺炎患者肺组织中的表达及其意义。方法:选取2010年2月至2013年12月在我院就诊的72例经支气管镜肺活检的不同类型的特发性间质性肺炎患者的组织标本,对其转化生长因子-β1表达程度进行评定。结果:寻常型(普通型)、非特异性、脱屑性、急性等ⅡP、呼吸性细支气管炎并间质性肺疾病以及隐原性机化性肺炎患者肺组织中TGF-β1表达强度评分均显著高于对照组;脱屑性ⅡP和呼吸性细支气管炎并间质性肺疾病患者肺组织中TGF-β1表达强度评分均显著高于其他类型ⅡP患者;非特异性ⅡP、急性ⅡP、淋巴细胞性ⅡP以及隐原性机化性肺炎组患者肺组织中TGF-β1表达强度评分均显著低于寻常型(普通型)ⅡP组;隐原性机化性肺炎、淋巴细胞性ⅡP组患者肺组织中TGF-β1表达强度评分分别为(0.93±0.34)分、(0.82±0.27)分,显著低于急性ⅡP组患者的(1.64±0.05)分。差异均有统计学意义(P<0.05)。结论:TGF-β1表达过度可能是ⅡP患者的重要特征,在肺纤维化的过程中发挥着重要作用,但在不同类型ⅡP中的作用机制并不相同。     

Antibodies to cytokeratin-8 in patients with different lung pathology

Antibodies to cytokeratin-8 were detected by enzyme immunoassay (EIA) in sera of 135 patients with cryptogenic fibrosing alveiolitis, different rheumatic diseases, sarcoidosis and exogenous allergic alveolitis, 109 patients with inflammatory lung diseases and 74 donors of the Moscow Blood Transfusion Station. The results revealed that The frequency of positive EIA reactions among the donors was 7%, while in the group of patients with rheumatic diseases--from 5.9% (scleroderma) to 42.9% (fibrosing alveolitis). Positive reactions also occurred in patients with exogenous allergic alveolitis and sarcoidosis. In the group of patients with chronic inflammatory lung diseases, i.e. in pathologies of non-autoimmune origin, positive reactions occurred in 13.3-33.3% of cases. To improve diagnostics and to disclose the mechanisms of pathogenesis, more detailed study of anticytokeratin antibodies in cases of interstitial lesions and chronic inflammatory lung diseases are necessary.     

Cellular events in alveolitis and the evolution of pulmonary fibrosis

"Alveolitis", as opposed to "pneumonia" sensu strictiori, is a term used to denote diffuse inflammatory changes of the pulmonary parenchyma, excluding those that result from local bacterial, fungal or other extracellular microbial growth. The various types of alveolitis are classified according to their histological characteristics and range from "luminal phagocytic" or "mural lymphoplasmacellular" and "exudative" to "fibrosing" alveolitis. In this overview, various exogenous and endogenous causes of different types of alveolitis, and the cellular events in their pathogenesis are briefly discussed to illustrate the complex mechanisms involved. Particular emphasis is placed on the possible transition from diffuse exudative to fibrosing alveolitis. It appears that pulmonary fibrosis, which is usually patchy rather than truly diffuse, does not have a uniform pathogenesis. Besides the possibility of a certain degree of a diffuse fibrosis three major pathways are evident: (1) granulation tissue budding into alveolar lumina (luminal fibrosis) (2) exudate incorporation into alveolar walls (mural fibrosis) and--at least equally important--(3) so-called collapse (atelectatic) induration (obliterative-interseptal fibrosis), a process that has largely been neglected so far.     

Lung surfactant in subacute pulmonary disease

Pulmonary surfactant is a surface active material composed of both lipids and proteins that is produced by alveolar type II pneumocytes. Abnormalities of surfactant in the immature lung or in the acutely inflamed mature lung are well described. However, in a variety of subacute diseases of the mature lung, abnormalities of lung surfactant may also be of importance. These diseases include chronic obstructive pulmonary disease, asthma, cystic fibrosis, interstitial lung disease, pneumonia, and alveolar proteinosis. Understanding of the mechanisms that disturb the lung surfactant system may lead to novel rational therapies for these diseases.     

Anorexigen-induced pulmonary hypertension and the serotonin (5-HT) hypothesis: lessons for the future in pathogenesis

Pulmonary surfactant is a surface active material composed of both lipids and proteins that is produced by alveolar type II pneumocytes. Abnormalities of surfactant in the immature lung or in the acutely inflamed mature lung are well described. However, in a variety of subacute diseases of the mature lung, abnormalities of lung surfactant may also be of importance. These diseases include chronic obstructive pulmonary disease, asthma, cystic fibrosis, interstitial lung disease, pneumonia, and alveolar proteinosis. Understanding of the mechanisms that disturb the lung surfactant system may lead to novel rational therapies for these diseases.     

Fibrosing Alveolitis Associated with Renal Tubular Acidosis

The discovery of a case of renal tubular acidosis and fibrosing alveolitis led to the investigation of 19 further patients. Abnormal pulmonary function tests were found in a further four patients with overt renal tubular acidosis and in four out of eight patients with “incomplete” renal tubular acidosis. The response to an ammonium chloride test in seven patients with cryptogenic fibrosing alveolitis was normal. Those patients with a defect of both renal acidification and pulmonary gas transfer had concurrent autoimmune diseases such as Sjögren''s syndrome and primary biliary cirrhosis. It is suggested that the renal and pulmonary abnormalities may be part of a systemic disorder capable of affecting many organs. Moreover, hyperglobulinaemia and autoantibodies in these patients further suggests that immunological mechanisms are concerned in the pathogenesis of these abnormalities.     

Proportional analysis of respiratory cells obtained by bronchoalveolar lavage.

Bronchoalveolar lavage was performed during fibreoptic bronchoscopy in 17 patients with biopsy-proven interstitial lung disease and in 12 control subjects who had focal lesions in the lung. The volume of fluid recovered was unrelated to disease activity or diagnosis. In the control subjects alveolar macrophages represented over 95% of the lavaged cells. The proportion of lymphocytes in the lavaged cells enabled a natural division of the diffuse interstitial lung diseases into two categories: active sarcoidosis, indicated by a large proportion of lymphocytes but a normal proportion of polymorphonuclear leukocytes; and idiopathic pulmonary fibrosis and asbestosis, indicated by a normal proportion of lymphocytes but a variable proportion of polymorphonuclear leukocytes. Bronchoalveolar lavage is a safe and well tolerated method for evaluating the role of alveolitis in diffuse interstitial lung disease through the sampling of respiratory alveolar cells.     

What causes cryptogenic fibrosing alveolitis? A case-control study of environmental exposure to dust.

OBJECTIVE--To investigate the role of occupational and domestic exposure to dust in the aetiology of cryptogenic fibrosing alveolitis. DESIGN--Matched case-control study. SUBJECTS--40 Patients with cryptogenic fibrosing alveolitis and 106 community controls matched for age and sex who responded to a questionnaire. MAIN OUTCOME MEASURE--Responses to self administered questionnaire asking about lifetime exposure to dust, animals, and smoke at home and at work. RESULTS--The patients with cryptogenic fibrosing alveolitis were more likely to report occupational exposure to metal dust (matched odds ratio 10.97 (95% confidence interval 2.30 to 52.4), p less than 0.001) or wood dust (2.94 (0.87 to 9.90), p = 0.08), to have worked with cattle (10.89 (1.24 to 96.0), p = 0.01), and to have lived in a house heated by a wood fire (12.55 (1.04 to 114), p = 0.009). A history of smoking and social class based on occupation were not significantly related to disease state. CONCLUSION--Environmental exposure to dust may be an important factor in the aetiology of cryptogenic fibrosing alveolitis.     

Diffuse alveolar damage syndrome associated with amiodarone therapy.

Amiodarone is an effective antiarrhythmic that has been used in Europe for over a decade and has been available for investigational use in North America for a shorter time. It has several well recognized side effects. Recent reports have related pulmonary disorders to the use of this drug; fibrosing alveolitis has been found by lung biopsy. Amiodarone''s toxicity to the lung does not appear to be dose-related. Besides cessation of amiodarone administration, management of this complication includes steroid therapy. A case is described of nonspecific diffuse alveolar damage syndrome in a patient who had received amiodarone.     

Anti-Jo-1 antibody: a marker for myositis with interstitial lung disease.

An autoantibody known as anti-Jo-1 antibody is found in 25% of patients with myositis. Its prevalence in patients with both myositis and cryptogenic fibrosing alveolitis was 68% (13 out of 19 patients), compared with 7.5% in patients with myositis alone (four of 53) and 3% in patients with cryptogenic fibrosing alveolitis alone (two of 62). Anti-Jo-1 antibody may be useful in indicating patients with myositis and cryptogenic fibrosing alveolitis. Raynaud''s phenomenon, the sicca syndrome, and mild arthritis are also often part of the syndrome.     

结缔组织病伴发疾病分析

目的：对结缔组织病与其常见伴发疾病进行研究分析,探讨肿瘤等疾病与与结缔组织病的相关性。方法：收集确诊有结缔组织病患者共333例,对其临床资料并进行回顾性统计分析。结果：本文中333例结缔组织病中发生肺间质病变79例（23.7%）,发生肿瘤8例（2.4%）,出现肾损害有124例（37.2%）。结论：间质性肺病、肿瘤、肾损害在结缔组织病患者中占一定的比例,其机制可能与结缔组织病本身的病理生理改变、外源性因素等共同作用所致。     

Environmental injury of the lung: role of humoral mediators.

Environmental lung injury may take the form of acute tracheobronchitis, asthma, pulmonary edema, chronic bronchitis, emphysema, allergic pneumonitis, fibrosing alveolitis, pleurisy, and neoplastic disease. Environmental factors eliciting these responses include irritant gases and fumes, oxidants, organic allergens, inorganic dust, bacterial enzymes, and high partial pressures of oxygen. The basic pulmonary reactions to these toxic agents--bronchoconstriction, vasoconstriction, increased vascular permeability, inflammation, carcinogenesis--may be mediated, aggravated, or modulated by biologically active substances. These humoral agents include biogenic amines (e.g. histamine): peptides (e.g., bradykinin, vasoactive intestinal peptide, and spasmogenic lung peptide); enzymes (e.g., proteases, superoxide dismutase, and mixed function oxidases); and acidic lipids (e.g., prostaglandins, prostaglandin endoperoxides, and thromboxanes).     

A case of resectable lung adenocarcinoma associated with sarcoidosis

A 71-year-old woman with uveitis was referred to our hospital for further examination of the possible underlying diseases. In roentgenological examination with plain X-ray and CT scan, hilar and mediastinal lymphadenopathy and a mass shadow in the right upper lung field was observed, whereas fibrotic changes were not obvious in both lung fields. Transbronchial lung biopsy with fiberoptic bronchoscope revealed granulomatous interstitial pneumonia. CD4-positive lymphocytes were increased in bronchoalveolar lavage. The patient was diagnosed as having sarcoidosis. Subsequently, right upper lobectomy was performed, and Stage I lung adenocarcinoma was diagnosed. The patient is under follow up without medication and the disease has been stable for two years. A relationship between epithelioid granulomatosis and malignant diseases is discussed and a review of the literature is given. Since it is still controversial as to the incidence of malignant diseases in sarcoidosis patients, it is important to accumulate data on these associations.     

When is pneumonia not pneumonia: a clinicopathologic study of the utility of lung tissue biopsies in determining the suitability of cadaveric tissue for donation

Healthcare-associated pneumonia (HCAP) represents a major diagnostic challenge because of the relatively low sensitivity and specificity of clinical criteria, radiological findings, and microbiologic culture results. It is often difficult to distinguish between pneumonia, underlying pulmonary disease, or conditions with pulmonary complications; this is compounded by the often-subjective clinical diagnosis of pneumonia. We conducted this study to determine the utility of post-mortem lung biopsies for diagnosing pneumonia in tissue donors diagnosed with pneumonia prior to death. Subjects were deceased patients who had been hospitalized at death and diagnosed with pneumonia. Post-mortem lung biopsies were obtained from the anatomic portion of the cadaveric lung corresponding to chest radiograph abnormalities. Specimens were fixed, stained with hematoxylin and eosin, and read by a single board-certified pathologist. Histological criteria for acute pneumonia included intense neutrophilic infiltration, fibrinous exudates, cellular debris, necrosis, or bacteria in the interstitium and intra-alveolar spaces. Of 143 subjects with a diagnosis of pneumonia at time of death, 14 (9.8 %) had histological evidence consistent with acute pneumonia. The most common histological diagnoses were emphysema (53 %), interstitial fibrosis (40 %), chronic atelectasis (36 %), acute and chronic passive congestion consistent with underlying cardiomyopathy (25 %), fibro-bullous disease (12 %), and acute bronchitis (11 %). HCAP represents a major diagnostic challenge because of the relatively low sensitivity and specificity of clinical criteria, radiological findings, and microbiologic testing. We found that attending physician-diagnosed pneumonia did not correlate with post-mortem pathological diagnosis. We conclude that histological examination of cadaveric lung tissue biopsies enables ascertainment or rule out of underlying pneumonia and prevents erroneous donor deferrals.     

Alpha-chain Disease with Pulmonary Manifestations

A case of alpha-chain disease of the pulmonary type is described in a man presenting with dyspnoea, mottling on chest x-ray picture, and a CO-transfer factor of 36%, suggestive of fibrosing alveolitis. The serum IgA consisted entirely of abnormal alpha chains devoid of light chains. This protein had the unusual property of reacting by immunofluorescence with rat mitochondria but not with human issues or with those of other species. Postmortem examination showed enlarged mediastinal lymph nodes with no evidence of malignancy or fibrosing alveolitis.