肺活检在特发性肺纤维化诊断中的应用

特发性肺纤维化(IPF)是特发性间质性肺疾病中最常见、预后最差的类型.早诊早治是改善患者预后的关键措施.对于胸部高分辨率CT(HRCT)表现不是典型的普通型间质性肺炎(UIP)时,通常需要进行肺活检辅助诊断.外科肺活检可获取到足够的样本,是获得肺组织学样本的金标准.但外科肺活检可能导致IPF患者病情急性加重,甚至死亡....     

Diagnosing fibrotic lung disease: When is high‐resolution computed tomography sufficient to make a diagnosis of idiopathic pulmonary fibrosis?

Idiopathic pulmonary fibrosis (IPF), a progressive and fatal diffuse parenchymal lung disease, is defined pathologically by the pattern of usual interstitial pneumonia (UIP). Unfortunately, a surgical lung biopsy cannot be performed in all patients due to comorbidities that may significantly increase the morbidity and mortality of the procedure. High-resolution computed tomography (HRCT) has been put forth as a surrogate to recognize pathological UIP. The quality of the HRCT impacts the ability to make a diagnosis of UIP and varies based on the centre performing the study and patient factors. The evaluation of the HRCT includes assessing the distribution and predominance of key radiographical findings, such as honeycomb, septal thickening, traction bronchiectasis and ground glass attenuation lesions. The combination of the pattern and distribution is what leads to a diagnosis and associated confidence level. HRCT features of definite UIP (subpleural, basal predominant honeycomb with septal thickening, traction bronchiectasis and ground glass attenuation lesions) have a high specificity for the UIP pathological pattern. In such cases, surgical lung biopsy can be avoided. There are caveats to using the HRCT to diagnose IPF in isolation as a variety of chronic pulmonary interstitial diseases may progress to a UIP pattern. Referral centres with experience in diffuse parenchymal lung disease that have multidisciplinary teams encompassing clinicians, radiologists and pathologists have the highest level of agreement in diagnosing IPF.     

Acute exacerbation of chronic interstitial pneumonia: high-resolution computed tomography and pathologic findings

PURPOSE: To review the high-resolution computed tomography (CT) and histologic findings of acute exacerbation of chronic interstitial pneumonia and to assess the potential value of CT and histologic findings in predicting prognosis. MATERIALS AND METHODS: The study included 24 patients with clinical and histologic diagnosis of acute exacerbation of chronic interstitial pneumonia who underwent CT within 1 month before biopsy or autopsy. The final diagnosis was acute exacerbation of idiopathic pulmonary fibrosis (n=12), usual interstitial pneumonia associated with connective tissue disorders (n=5), idiopathic nonspecific interstitial pneumonia (n=4), and nonspecific interstitial pneumonia associated with connective tissue disorders (n=3). RESULTS: The main CT findings consisted of bilateral ground-glass opacities (100%) and consolidation (71%) superimposed on a reticular pattern. The ground-glass opacities and/or consolidation were diffuse in 54% of the cases, multifocal in 21%, and peripheral in 25%. The histologic patterns of acute injury consisted of diffuse alveolar damage (n=20), acute organizing pneumonia (OP) (n=3), and extensive fibroblastic foci (n=1). Eight (33%) patients survived the acute episode, including all 3 patients with OP and the patient with extensive fibroblastic foci (P=0.01). The survivors included 3 of 13 (23%) patients with diffuse parenchymal opacification, 2 of 5 (40%) patients with multifocal, and 3 of 6 (50%) patients with peripheral opacification on CT. CONCLUSIONS: The CT findings of acute exacerbation of chronic interstitial pneumonia consist of diffuse, multifocal, or peripheral parenchymal opacification superimposed on reticulation. Histologic findings of OP are superior to CT in predicting prognosis.     

Histopathologic features and outcome of patients with acute exacerbation of idiopathic pulmonary fibrosis undergoing surgical lung biopsy

STUDY OBJECTIVES: To define the clinicopathologic features and outcome of acute exacerbation in patients with idiopathic pulmonary fibrosis (IPF) undergoing surgical lung biopsy. DESIGN: Retrospective, single-center study. SETTING: Tertiary care, referral medical center. PATIENTS: Seven patients with acute exacerbation of IPF who underwent surgical lung biopsy. RESULTS: The median age of these seven patients was 70 years (range, 59 to 74 years); two were women. Five patients had a smoking history and included two current smokers. All patients were experiencing an exacerbation of dyspnea for a median duration of 14 days (range, 7 to 28 days) prior to presentation. In three of these patients, the acute deterioration was the presenting feature of IPF, while in the remaining four patients the diagnosis of IPF had previously been established. Chest radiography demonstrated bilateral mixed alveolar-interstitial infiltrates in all of them. CT revealed ground-glass opacities and consolidation bilaterally in all patients with associated peripheral honeycombing in six of them. Echocardiography was performed in six patients and demonstrated pulmonary hypertension in all. BAL fluid was obtained in five patients and revealed neutrophilia in all. Surgical lung biopsy showed diffuse alveolar damage (DAD) in five patients with associated collagen fibrosis and honeycomb changes typical of usual interstitial pneumonia (UIP). One biopsy showed a combination of UIP and organizing pneumonia, while one biopsy showed only DAD. Despite treatment with lung-protective ventilation strategies and high-dose systemic corticosteroids, six patients (86%) died during their hospitalization. CONCLUSIONS: Although IPF is typically associated with an insidious, slowly progressive clinical course, acute exacerbations occur and may be the presenting manifestation in some patients. In either situation, current management strategies including high-dose corticosteroid therapy appear to be relatively ineffective for these patients with acute exacerbation undergoing surgical lung biopsy.     

Potential limitations of clinical criteria for the diagnosis of idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitis

BACKGROUND: The need to perform surgical lung biopsy (SLB) in all cases of suspected idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitis (IPF/CFA) is controversial. The American Thoracic Society (ATS) and the European Respiratory Society (ERS) recently endorsed explicit clinical criteria for the diagnosis of IPF/CFA in the absence of SLB. Prior studies evaluating clinical criteria for the diagnosis of IPF/CFA have been limited in that either they were performed by clinicians with expertise in the diagnosis of IPF/CFA or they did not utilize explicit diagnostic criteria. We investigated the accuracy of the ATS/ERS criteria when applied in a general pulmonary medicine setting. OBJECTIVES: To determine the interobserver variability of clinical criteria for the diagnosis of IPF/CFA. METHODS: This was a retrospective, blinded evaluation by three board certified pulmonary physicians without extensive experience in the evaluation of IPF/CFA performed at a United States Army tertiary care academic medical center. Patients referred for surgical lung biopsy as part of a diagnostic evaluation of interstitial lung disease (ILD) were evaluated. The physicians reviewed high-resolution computed tomography scans of the chest (HRCT) and clinical data for each patient. The physicians were blinded to all other data and to the opinions of other study participants. Employing the histologic presence of usual interstitial pneumonia (UIP) coupled with appropriate clinical findings as the gold standard for a diagnosis of IPF/CFA we determined the accuracy and interobserver variability for a diagnosis of IPF/CFA based on HRCT alone and based on the ATS/ERS clinical criteria. RESULTS: The sensitivity and positive predictive value for a HRCT diagnosis of IPF/CFA were 71% each while specificity and negative predictive value were 67% each. For the ATS/ERS criteria sensitivity, specificity, positive predictive value and negative predictive value were 71, 75, 77 and 69%, respectively. The interobserver variability, expressed as a kappa coefficient, for HRCT and the ATS/ERS criteria were 0.59 and 0.53, respectively. CONCLUSIONS: Both HRCT and the ATS/ERS clinical criteria may lead to misdiagnosis of patients with ILD. Further studies are needed to fully characterize the accuracy of these tests when applied in a routine pulmonary medicine practice setting.     

Spectrum and diagnosis of idiopathic pulmonary fibrosis

OBJECTIVE: To study the clinical profile of patients with idiopathic pulmonary fibrosis (IPF) and methods used for diagnosis. METHODS: Prospective analysis of symptoms, signs, radiology and lung biopsy of patients freshly diagnosed to have IPF over a 16-month period. RESULTS: During the study period, 76 patients (35 men) with a mean age of 50.6 +/- 11.9 years were diagnosed to have IPE Breathlessness (98.6%) and dry cough (92.1%) were the most common presenting symptoms. Transbronchial lung biopsy (TBLB) was performed in 38 (50%) patients. Histopathological examination revealed features consistent with IPF in 35 (92.1%) patients; two of the remaining three patients underwent open lung biopsy. Other patients were diagnosed based on clinical features and high resolution chest tomography (HRCT) findings. HRCT was performed in 69 (90.8%) patients; all had features suggestive of diffuse interstitial fibrosis. CONCLUSION: IPF is diagnosed more commonly now than in the past. Indian patients may be developing the disease a decade earlier than their counterparts in the West. TBLB and HRCT are useful in establishing diagnosis. IPF should be considered a distinct clinical entity rather than a diagnosis of exclusion.     

Do high-resolution CT findings of usual interstitial pneumonitis obviate lung biopsy? Views of pulmonologists

BACKGROUND: High-resolution CT (HRCT) of the lungs has become an essential component to evaluate patients with diffuse lung disease. Little is known, however, about the current practices of pulmonologists caring for patients with these complex conditions, and, in particular, whether HRCT can obviate the need for surgical lung biopsy. OBJECTIVES: To investigate the practices of pulmonologists concerning the acceptability of a HRCT diagnosis in lieu of lung biopsy in diffuse lung disease. METHODS: We asked practicing pulmonologists among membership of the American College of Chest Physicians whether HRCT results could replace lung biopsy in 16 diffuse lung diseases. Responses were examined in light of published evidence, practice guidelines, and certain practice parameters. RESULTS: Two hundred and thirty (52.6%) of 437 eligible physicians responded. Sixty-seven percent (67%) of respondents accepted HRCT diagnosis for idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) despite their awareness of guidelines recommending histological diagnosis. Most would not accept a radiologic diagnosis for lymphangioleiomyomatosis (LAM; 37%) or eosinophilic granuloma (Langerhans' cell histiocytosis, LCH; 19%), even though CT findings are frequently characteristic. Responses were similar by type of clinical practice and recency of fellowship training. Chest physicians who referred patients for HRCT more frequently were more likely to accept HRCT diagnosis (p=0.008) and those who had higher self-ratings of proficiency in reading HRCT (p = 0.004) were more likely to believe HRCT often suggests specific diagnosis. CONCLUSIONS: Most US pulmonologists will accept an HRCT diagnosis of IPF/UIP without lung biopsy, but are reluctant to do so for most other diffuse lung conditions including LAM and LCH.     

The accuracy of the clinical diagnosis of new-onset idiopathic pulmonary fibrosis and other interstitial lung disease: A prospective study

STUDY OBJECTIVES: Presently, surgical (open or thoracoscopic) lung biopsy (SLB) is the gold standard for the diagnosis of new-onset idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs). The accuracy of a clinical diagnosis of IPF and other subsets of ILD has never been established in prospective studies. We investigated the accuracy and validity of a clinical diagnosis of IPF and ILD other than IPF. DESIGN: Prospective, independent evaluation of patients and clinical data by an ILD expert, of chest radiographic and high-resolution computed tomography (HRCT) features by a chest radiologist, and of histologic features of lung biopsy by a pulmonary pathologist in consecutive patients referred for a diagnostic evaluation of ILD. SETTING: Tertiary university medical center with recognized expertise in management of ILD. PATIENTS: Community patients referred for further definitive diagnostic evaluation of new-onset, untreated nonspecific ILD. INTERVENTION: By comparing the histologic features of SLB in 59 patients consecutively referred for further diagnostic evaluation of new-onset ILD with the clinical and radiologic diagnoses, we determined the sensitivity and specificity of clinical diagnosis and radiologic diagnosis (based on chest radiograph and HRCT features alone) of IPF and ILD other than IPF. A specific clinical diagnosis was independently made by the ILD expert after a thorough clinical assessment that included evaluation of an HRCT scan and bronchoscopic findings. The chest radiographs and HRCT scans were separately reviewed by the chest radiologist, who made a radiologic diagnosis independently. All patients underwent SLB within a month of preoperative "clinical" diagnosis. The clinician's and radiologist's diagnoses were then compared with the gold standard of histologic diagnosis. Measurements and results: Prior to the clinical evaluation at our center, 85% of patients who underwent SLB had nondiagnostic transbronchial biopsy. The diagnosis of IPF and ILD other than IPF was accurately made by clinical features alone in 62% of cases. The correct radiographic diagnosis of non-IPF ILD was made in 58% of the cases. The sensitivity and specificity of the clinical diagnosis of ILD other than IPF were 88.8% and 40%, respectively. The sensitivity and specificity of the radiographic diagnosis of ILD other than IPF were 59% and 40%, respectively. However, the sensitivity and specificity of the diagnosis of IPF on clinical grounds were 62% and 97%, respectively. The sensitivity and specificity of the radiologic diagnosis of IPF were 78.5% and 90%, respectively. CONCLUSIONS: In a center with recognized expertise in the management of ILD, the specificity of diagnosis of new-onset IPF based on a thorough clinical assessment or HRCT features alone is very high (97% and 90%, respectively), but the sensitivity is low (62% and 78.5%, respectively). Thus, not all patients with new-onset IPF require SLB for diagnosis, but a diagnosis of IPF will be missed in nearly one third of new-onset IPF cases despite evaluation by experts. The relatively low sensitivity and specificity of the diagnosis of ILD other than IPF also emphasizes that an SLB is indicated in patients with ILD in whom the diagnosis is unclear.     

Recent advances in radiology of the interstitial lung disease

Idiopathic interstitial pneumonias are currently classified into four categories of disease: usual, desquamative, and acute interstitial pneumonia, and nonspecific interstitial pneumonia and fibrosis. Usual interstitial pneumonia appears on high-resolution CT (HRCT) as patchy subpleural areas of ground-glass opacity, irregular lines, and honeycombing. Desquamative interstitial pneumonia presents as patchy subpleural areas of ground-glass opacity in middle and lower lung zones. Acute interstitial pneumonia presents as extensive bilateral airspace consolidation and patchy or diffuse bilateral areas of ground-glass opacity. Nonspecific interstitial pneumonia and fibrosis appears as patchy or diffuse areas of ground-glass opacity with associated areas of consolidation and irregular lines. In a subset of patients with diffuse lung disease (especially in those with chronic interstitial lung disease), accurate diagnosis can be made with HRCT findings only, without surgical biopsy. However, HRCT provides a lower level of confidence in the diagnosis of acute or subacute interstitial lung disease such as infection, diffuse alveolar damage, drug reaction, or hemorrhage. Additional expiratory HRCT scans and scans with patients prone help to narrow the differential diagnosis among various diseases and help diagnose or exclude subtle disease in the posterior part of the lung, respectively. HRCT provides a reproducible method for evaluating the global extent of disease. It also discriminates between fibrotic and reversible inflammatory diseases.     

Outcomes and safety of surgical lung biopsy for interstitial lung disease

STUDY OBJECTIVES: To determine the safety of surgical lung biopsy (SLB) in patients with interstitial lung disease (ILD), and specifically in those with idiopathic pulmonary fibrosis (IPF). DESIGN: Retrospective cohort. SETTING: Tertiary care university-affiliated military medical center. PATIENTS: Individuals undergoing SLB for suspected ILD. MEASUREMENTS AND RESULTS: We examined outcomes for subjects with a clinical diagnosis of ILD who had been designated to undergo SLB. Mortality (assessed at 30 and 90 days) following SLB represented the primary end point. Morbidity resulting from complications from SLB served as a secondary end point. The cohort included 83 patients (mean [+/- SD] age, 57.3 +/- 14.2 years; men, 57.8%). IPF was eventually diagnosed in slightly more than half of the subjects. Overall, 30-day and 90-day mortality rates were low (4.8% and 6.0%, respectively). Subjects with IPF did well with SLB (30-day mortality rate, 7.1%) and did not face a higher risk of either death or complications relative to individuals with non-IPF forms of ILD. The only predictors of perioperative mortality were either the need for mechanical ventilation (MV) at the time of SLB or being immunosuppressed prior to undergoing SLB. Excluding persons who met either criterion yielded an overall 90-day post-SLB mortality rate of 1.5% in persons with IPF. Approximately 40% of patients in whom IPF was eventually diagnosed were initially thought to have another form of ILD. CONCLUSIONS: Persons with IPF tolerate SLB well. Requiring MV or being immunosuppressed is associated with an increased risk for death following SLB. Safety concerns should not preclude referral for SLB in patients who are clinically suspected of having IPF.     

Fatal acute exacerbation of idiopathic pulmonary fibrosis/usual interstitial pneumonia initially in the right lung after surgery lobectomy for left lung cancer]

A tumor was found in the left S10 in a chest CT scan of a 72-year-old male patient with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP). He underwent left lower lobectomy and resection of the hilar and mediastinal lymph nodes under video-assisted thoracoscopic surgery. The histopathological evaluation disclosed a well-differentiated squamous cell carcinoma (T1N0M0; stage IA) associated with UIP. On the sixth postoperative day, a severe hypoxemia (PaO2 48 mmHg) developed, and the chest CT showed diffuse ground glass opacity (GGO) in the right lung. A diagnosis of acute exacerbation of IPF/UIP was made, and steroid pulse therapy with cyclosporin A was started. However, despite this therapy, the diffuse GGO extended to both lung fields, and the patient died of respiratory failure 82 days later. The histopathology at autopsy demonstrated diffuse alveolar damage due to UIP that was consistent with acute exacerbation of IPF/UIP. It is suggested that the acute exacerbation of IPF/UIP could have been triggered by a high concentration of oxygen or mechanical lung injury during the patient's surgery.     

普通型间质性肺炎与非特异性间质性肺炎急性加重的临床与病理表现

目的 研究间质性肺疾病患者急性加重的临床和病理表现.方法 回顾性总结北京协和医院自1999年4月至2007年6月间经肺部病理活检证实的普通型间质性肺炎(UIP)和非特异性间质性肺炎(NSIP)急性加重患者各3例的临床资料.其中5例为急性加重前的间质性肺炎病理的结果,1例为急性加重后的尸检结果.结果 6例中男2例,女4例,年龄29～57岁(中位年龄51岁).急性加重前的病理表现:3例为UIP(1例为特发性,1例为皮肌炎继发,1例为结缔组织病继发),2例为NSIP(1例为特发性,1例为皮肌炎继发),1例尸检为弥漫性肺泡损伤合并NSIP(皮肌炎继发).6例中2例在急性加重前1周曾行胸腔镜肺活检术,5例发热,2例白细胞数增高,5例中性粒细胞比例升高.6例的痰培养和血培养无阳性发现.急性加重时氧合指数为200 mm Hg(四分位间距为158～237 mm Hg,1 mm Hg=0.133 kPa),4例ESR增快,2例C反应蛋白升高.胸部CT示在原有病变基础上出现磨玻璃影和实变影.5例使用糖皮质激素35～1000 mg/d,2例使用静脉人血丙种球蛋白,住院期间死亡4例,3例使用有创机械通气的患者均死亡,存活出院者1例稳定,1例好转,其后2例均失访.结论 UIP和NSIP都可出现急性加重,临床表现为突然出现的呼吸困难及发热,无特异性,诱因不清,广谱抗生素治疗无反应,大剂量糖皮质激素及静脉人血丙种球蛋白治疗可能有效.     

HRCT of fibrosing lung disease

The use of high‐resolution computed tomography (HRCT) has brought increased diagnostic discrimination to the evaluation of lung disease, particularly fibrosing lung diseases. Once the presence of a predominantly fibrosing lung disease has been established on evaluation of a HRCT, a stepwise approach is proposed that can refine the potential HRCT diagnoses from a list of over 100 different interstitial lung diseases to one of only five fibrosing lung diseases. Within the category of the fibrosing lung diseases, the recognition of idiopathic pulmonary fibrosis (IPF) is key. IPF is the most prevalent idiopathic interstitial pneumonia and has a mortality greater than any of the other diffuse lung diseases. Several diagnostic dilemmas are explored including challenges with the recent IPF diagnosis and management guidelines (2011), as well as with the ‘difficult to characterize’ fibrosing diseases such as smoking‐related lung fibrosis, unclassifiable disease and acute exacerbations of fibrosing lung disease.     

Diagnostic utility of surgical lung biopsies in elderly patients with indeterminate interstitial lung disease

Background and objective

Idiopathic pulmonary fibrosis (IPF) is increasingly diagnosed by clinical and computed tomography (CT) criteria; however, surgical lung biopsy (SLB) may still be required in patients who lack definite CT features of usual interstitial pneumonia (UIP). We reviewed a cohort of elderly patients who underwent SLB, to evaluate the benefit of SLB in diagnosing idiopathic interstitial pneumonia (IIP).

Methods

We searched the pathology records of Mayo Clinic for ambulatory patients at least 75 years old, who underwent SLB between 2000 and 2012 for indeterminate IIP. Histologic slides were reviewed and clinical data were extracted from the record.

Results

A total of 55 patients (35 male) were enrolled. Median (interquartile range) age was 77 (76–80) years. Forced vital capacity was 70 (61–76)% and diffusing capacity of the lungs for carbon monoxide was 48 (42–54)% of predicted. In total, 37 (67%) patients had IPF, including 61% of those with HRCT findings inconsistent with UIP. Thirty‐day mortality was 10% and 90‐day mortality was 15%.

Conclusion

The high mortality rate of SLB complicates the risk–benefit analysis in elderly patients with IIP. The expected value of the SLB is probably highest when the HRCT features are inconsistent with UIP, due to the frequent (39%) retrieval of patterns other than UIP.

     

特发性肺纤维化的综合诊断进展

特发性肺纤维化是最常见的一种特发性间质性肺炎,组织病理表现为普通型间质性肺炎,临床表现为进行性呼吸困难伴有刺激性干咳,确诊依赖于外科肺活检。但肺活检风险大、费用高,不易被患者接受。近年来研究发现综合HRCT、血清标志物、以及肺功能、支气管肺泡灌洗液等检查,可以对IPF作出早期准确的诊断。本文将从上述几个方面作一介绍。     

Idiopathische Lungenfibrose

The diagnosis of idiopathic pulmonary fibrosis (IPF) is based on a usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) in patients not subjected to surgical lung biopsy or specific combinations of HRCT with histopathological patterns after exclusion of known causes of interstitial lung disease. The diagnostic work-up should also include initial lung function and the diagnosis of comorbidities. The interdisciplinary discussion of clinical, radiological and histological data is essential.     

Clinical impact of the radiological indeterminate for usual interstitial pneumonia pattern on the diagnosis of idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a fatal lung disease associated with significant morbidity and mortality. The international clinical practice guidelines for the diagnosis of IPF have recently been revised.MethodsIn this single-center retrospective study conducted between June 2006 and March 2018, 27 patients with a newly classified indeterminate for usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) who had undergone surgical lung biopsy were enrolled at the Japanese Red Cross Medical Center. Clinical and pathological characteristics and prognosis were retrospectively analyzed from patient records.ResultsOn the basis of multidisciplinary discussion (MDD), IPF was diagnosed in six patients (22%), unclassifiable interstitial pneumonia in 5 (19%), chronic hypersensitivity pneumonitis in 10 (37%), collagen vascular disease-associated interstitial lung disease in 5 (19%), and lymphoproliferative disorder in 1 (4%) patient. Ground-glass opacity, peribronchovascular distribution, upper or middle lobe distribution, mosaic attenuation, consolidation patterns, and honeycombing were found on HRCT. Histological UIP or probable UIP was observed in seven patients. The median survival time from the initial visit was 2770 days (92.3 months). There was a significant difference in survival time in the GAP stage and honeycombing on HRCT according to the log-rank test.ConclusionsPatients with an indeterminate for UIP pattern on HRCT were more likely to have non-IPF than IPF through pathological diagnosis and MDD. GAP stage and honeycombing on HRCT may be significant risk factors for all-cause mortality.     

Acute exacerbation of interstitial pneumonia other than idiopathic pulmonary fibrosis

BACKGROUNDS: Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) is increasingly recognized as a relatively common and highly morbid clinical event. However, clinical data on AE in non-IPF interstitial pneumonia are sparse. This study was performed to find the frequency, clinical features, and outcome of AE in non-IPF interstitial pneumonia. METHODS: Retrospective analysis of 10 patients who satisfied the modified Akira criteria for AE during follow-up of 74 patients with surgical lung biopsy-confirmed idiopathic nonspecific interstitial pneumonia (I-NSIP) and 93 patients with biopsy-confirmed interstitial pneumonia associated with collagen vascular disease (CVD-IP). RESULTS: AE occurred in six patients with I-NSIP (1-year frequency, 4.2%) and in four patients with CVD-IP (rheumatoid arthritis [RA], n = 3; scleroderma, n = 1), with 1-year frequency of 3.3%. Median age was 58 years (range, 47 to 75); six patients were female. AE occurred in two patients immediately after surgical biopsy. Median duration of acute symptom before hospital admission was 10 days (range, 1 to 30). Median ratio of Pao(2) to the fraction of inspired oxygen (Fio(2)) was 172 (range, 107 to 273), and Pao(2)/Fio(2) ratio was < 200 in six patients. Surgical lung biopsy performed at the time of AE in two patients revealed diffuse alveolar damage superimposed on nonspecific interstitial pneumonia pattern. Four patients with I-NSIP survived to discharge and were followed up for 24 months (range, 6 to 121). CONCLUSION: AE occurred in the patients with I-NSIP with apparently better prognosis. In patients with CVD-IP, AE occurred mostly with RA-usual interstitial pneumonia in our small series with poor outcome.     

A case of idiopathic pulmonary fibrosis with histology of usual interstitial pneumonia that responded to pulse therapy followed by combined immunosuppression with prednisolone and azathioprine]

A 64-year-old woman who was admitted with cough and dyspnea showed severe hypoxemia and interstitial lung shadows. The clinical diagnosis was idiopathic interstitial pneumonia (synonymous with idiopathic pulmonary fibrosis in the United States), since there were no specific immunological or bacteriological findings. No clinical signs or laboratory data compatible with collagen disease were observed. Methylprednisolone pulse therapy was given followed by prednisolone (0.8 mg/kg) and azathioprine (15 mg/kg). Marked improvement of hypoxia, chest X-ray and spirometry results was observed after five weeks. Histological examination of an cases of residual interstitial shadow obtained by open lung biopsy revealed usual interstitial pneumonia. Tapering of the immunosuppressant drugs led to a recurrence 3 months later, which was controlled by reintroduction of the same regimen. Therefore, only prednisolone was tapered, and data obtained in an outpatient clinic 6 months after the recurrence were as follows: %VC 108%, %DLco 72%, PaO2 80 Torr. The value of this regimen for acute IPF or exacerbation of IPF is suggested because of its life-saving effects.     

涎液化糖链抗原-6在老年特发性肺纤维化诊治中的应用

目的探讨涎液化糖链抗原-6（kerbs von den lungen-6, KL-6）在老年特发性肺纤维化（idiopathic pulmonary fibrosis, IPF）诊断和治疗中的评估价值。 方法选取2018年7月至2019年11月牡丹江医学院附属红旗医院收治的普通型间质性肺炎型IPF患者68例，其中老年患者36例（老年IPF组）、非老年患者32例（非老年IPF组），另择同期老年健康体检者32例（老年健康组）作为对照。采用酶联免疫吸附试验测定血清KL-6表达水平，记录所有IPF患者的肺功能指标，并对其普通型间质性肺炎病变程度进行评估。比较各组血清KL-6的表达水平及肺部高分辨率CT（HRCT）评分，分析KL-6与肺功能指标和肺部HRCT评分的相关性。多组间的比较采用方差分析（进一步两两比较采用LSD-t检验）或秩和检验，计数资料的比较采用χ²检验；相关关系采用Pearson相关分析或Spearman秩相关分析。 结果3组患者KL-6表达水平的差异有统计学意义（F=63.425，P<0.05），其中老年IPF组明显高于非老年IPF组和老年健康组（P<0.01）。ROC曲线显示，KL-6诊断老年IPF的临界值为516.21 U/ml，此时敏感度和特异度最高，分别为94.4%和87.5%。无论是老年IPF组还是非老年IPF组，急性加重患者血清KL-6表达水平均明显高于稳定患者（t=2.843、2.215，P<0.05或0.01）；老年IPF组中急性加重患者血清KL-6表达水平均明显高于非老年IPF组（t=2.657，P<0.05）。相关分析显示，无论是68例IPF患者还是老年IPF组患者，其KL-6水平与HRCT评分均呈正相关（r=0.748、0.699，P<0.01）。老年IPF患者血清KL-6表达水平与部分限制性通气功能和弥散功能指标呈负相关（r=-0.515、-0.393、-0.384，P<0.05）。 结论血清KL-6对诊断IPF有一定临床意义，尤其对于老年患者具有较高的诊断敏感度及特异度，且与疾病严重程度及治疗效果呈现一定相关性。