1、Conception of ILD(DPLD)ILD is a spectrum of non-infectious,non-neoplastic diseases involving predominately the alveolar wall and perialveolar tissue and surrounding architecture.DPLD(Diffuse Parenchymal Lung Disease):bronchioles and parenchymaMedical TerminologyInterstitial lung disease（ILD）间质性肺病Dif
2、fuse parenchymal lung disease(DPLD)弥漫性肺实质肺病Idiopathic interstitial pneumonia（IIP）特特发性间质性肺炎发性间质性肺炎Idiopathic pulmonary fibrosis（IPF）特发特发性肺纤维化性肺纤维化Usual interstitial pneumonia(UIP)普通性间普通性间质性肺炎质性肺炎Non-specific interstitial pneumonia(NSIP)非特异性间质性肺炎Cryptogenic organizing pneumonia（COP）隐原性机化性肺炎Acute inter
3、stitial pneumonia(AIP)急性间质性肺炎Desquamative interstitial pneumonia(DIP)脱屑性间质性肺炎Respiratory bronchiolitis-associated interstitial lung disease(RB-ILD)呼吸细支气管炎间质性肺炎Lymphocytic interstitial pneumonia(LIP)淋巴细胞性间质性肺炎Granulomatous肉芽肿的Sarcoidosis结节病结节病Lymphangioleiomyomatosis淋巴管平滑肌瘤Histiocytosis(HX)组织细胞增多症Ret
4、icular网格状Nodule(nodular)结节Ground glass opacity(GGO)磨(毛)玻璃影Bronchiectasis支气管扩张Honeycombing蜂窝Diffusion capacity弥散量Bronchoalveolar lavarge(BAL)肺泡灌洗Transbronchoscopic lung biopsy(TBLB)经气管镜肺活检Crackle爆裂音 Classification of ILD by ATS/ERS 2002IDIOPATHIC INTERSTITIAL PNEUMONIA(IIP)GRANULOMATOSISsarcoidosisHy
5、persensitive pneumonitisWegenersgranulomatosis,RARE ILDalv.proteinosisalv.hemorrhage-nephritis syndromeLangerhans cell histiocytosisLymphangioleiomyomatosis Idiopathic pulmonaryHemosiderosisChronic eosinophilic pneumoniaILD of known causesOccupational lung disease(pneumoconiosis)Drug-induced lung di
6、seaseConnective disease associated ILDILD of Unknown CausesAMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 165 2002EPIDEMIOLOGY ILD accounts for 100,000 hospital admissions yearly 15%of patients seen by pulmonologists nationwide.incidence and prevalence of ILD(5/100,000)in the US New
7、Mexico:overall prevalence of ILD was 80.9 per 100,000 in males and 67.2 per 100,000 in females incidence of ILD was 31.5 per 100,000 in men and 26.1 per 100,000 in women.Idiopathic pulmonary fibrosis represented 45%of the patient base.CLINICAL EVALUATION-HistoryLength Of Illness And Clinical CourseA
8、cute onset:days to weeksAcute interstitial pneumoniaAcute pneumonitis from collagen vascular disease(especially SLE)Cryptogenic organizing pneumoniaDrugsDiffuse alveolar hemorrhage（弥漫性肺抛出血）Eosinophilic lung disease（嗜酸性粒细胞肺病）Hypersensitivity pneumonitis（过敏性肺炎）Subacute:weeks to monthsCollagen vascular
9、 diseaseassociated ILDCryptogenic organizing pneumoniaDrugsSubacute hypersensitivity pneumonitisChronic:months to yearsIdiopathic pulmonary fibrosisChronic hypersensitivity pneumonitisCollagen vascular diseaseassociated ILDNonspecific interstitial pneumoniaOccupation-related lung disease(e.g.,silico
10、sis,asbestosis)CLINICAL EVALUATION-History Occupational and Environmental History:hypersensitivity pneumonitis,asbestosis Drug History:amiodaron，bleomycin，radiotherapy Age and Gender:young-sarcoidosis,IPF-50;women-lymphagioleiomyositosis（LM,淋巴管平滑肌瘤病）;men-pneumoconiosis（尘肺）Smoking History:high-eosino
11、philic granuloma,RB-ILD,IPF,asbestosis,；low-hypersensitive pneumonitis(HP过敏性肺炎),sarcoidosis Family History：familial IPF,LymphangioleiomyomatosisRespiratory Symptoms and SignsDyspnea:Progressive dyspnea,exertional/resting：the most common complaint.10%ILD may present with dyspnea with a normal chest r
12、adiograph.Suspection after exclusion of COPD,Pulmonary Embolism(肺栓塞).Cough:IPF,sarcoidosis,HP,COPChest Pain:CTD-ILD,pneomothorax with LMWheezing:sarcoidosis,HP,EP Bibasilar inspiratory crackles(爆裂音爆裂音):characteristic physical sign in ILD.Mechanism.Dry rales Digital clubbing,(杵状指)a marker of advanced
13、 fibrotic disease,often in IPF;CA suspected if after.Respiratory Symptoms and SignsLaboratory Investigation Autoantibodies(rheumatoid factor,antinuclear factors)CVD,IPF,WG,MPA,NSIP Serum angiotensin converting enzyme(血管紧张素转化酶抑制剂）:Sarcoidosis Eosinophilia:EP Antibasement membrane antibody:GPS Antineu
14、trophilic cytoplasmic antibody(ANCA,抗中性粒细胞胞浆抗体):WG,MPA Increased serum LDH:IPF,PAP,AIPRadiographic Features Grouns-glass opacipation磨玻璃影 Reticular or nodular网格/结节影 Honey-combing蜂窝影 Cyst囊 检查方式Plain CXRPlain CTHRCT：crucial for ILD diagnosis Alveolar filling pattern肺泡填塞征Nodular patternHoneycombReticula
15、r pattern-HPNodule-SarcoidosisHoney-combing蜂窝肺IPFGGO with thickened interlobular septa-crazy paving fashion(铺路石征）pulmonary alveolar proteinosisGround-glass opacity-idiopathic pulmonary hemosiderosisCyst囊LymphangioleiomyomatosisBronchoalveolar Lavage肺泡灌洗肺泡灌洗 Diagnosis:E35%eosinophilic pneumonia 嗜酸性粒细
16、胞肺炎 periodic acidSchiff(PAS)+:alveolar proteinosis肺泡蛋白沉积正 BAL lymphocytes(35%)sarcoidosis,HP,drug-induced ILD Response to therapy:lymphocytosisBAL-Alveolar proteinosisPhysiologic Testing Restriction限制性通气功能障碍 Diffusion defect弥散量降低 Preservation of airflow Increase in P(A-a)O2 Exercise-induced hypoxaem
17、ia低氧血症 Hyperventilation过度通气Pulmonary Function TestLung Biopsy-definitive diagnosis The final step in the diagnostic evaluation of a patient with ILD is to decide whether it is necessary to obtain lung tissue.Tranbronchial Lung Biopsy经气管镜肺活检 Percutaneous lung biopsy经皮肺活检 Video-assited thoracosopic lu
18、ng biopsy胸腔镜活检 Open lung biopsy开胸肺活检DiagnosisMulti-disciplinary approach to the diagnosis of ILD with Pulmonologist,radiologist and pathologist.IDIOPATHIC PULMONARY FIBROSIS(IPF)特发性肺纤维化IDIOPATHIC INTERSTITIAL PNEUMONIA(IIP)特发性间质性肺炎 The IIPs are a heterogeneous group of nonneoplastic disorders result
19、ing from damage to the lung parenchyma by varying patterns of inflammation and fibrosis.Idiopathic indicates unknown cause and interstitial pneumonia refers to involvement of the lung parenchyma by varying combinations of fibrosis and inflammation,in contrast to airspace disease typically seen in ba
20、cterial pneumonia.IIP的生存曲线IPF-Definition IPF is defined as a specific form of chronic,progressive fibrosing interstitial pneumonia of unknown cause,occurring primarily in older adults,limited to the lungs,and associated with the histopathologic and/or radiologic pattern of UIP defined below.The defi
21、nition of IPF requires the exclusion of other forms of interstitial pneumonia including other diopathic interstitial pneumonias and ILD associated with environmental exposure,medication,or systemic disease.Pathology of IPFPotential Risk Factors Cigarette smoking Environmental factor Microbial agents
22、 Gastroesophageal refluxClinical Features Symptoms&Signs Exertional dyspnea Cough Basilar crackle Lab&other testDEFINITION OF UIP PATTERNUIP征象UIP可能征象非UIP征象OTHER TESTS Pulmonary function test：restriction+diffusion defect with decreased compliance Arterial Blood Gas Analysis：Increased P(A-a)，Exertiona
23、l hypoxaemia with hypocapnia Bronchoscopy：tranbronchoscopic lung biopsy（TBLB，经气管镜肺活检）：exclusion of other diseases Lung biopsy：percutaneous，thoracoscopy，open-lungbiopsyDiagnostic CriteriaThe diagnosis of IPF requires the following:1.Exclusion of other known causes of ILD(e.g.,domestic and occupationa
24、l environmental exposures,connective tissue disease,and drug toxicity).2.The presence of a UIP pattern on HRCT in patients not subjected to surgical lung biopsy.3.Specific combinations of HRCT and surgical lung biopsy pattern in patients subjected to surgical lung biopsy.COMBINATION OF HRCT AND SURG
25、ICAL LUNG BIOPSY FOR THE DIAGNOSIS OF IPF IPF诊断标准未未IPF诊断标准未未IPF诊断标准未未Features associated with increased mortality in IPFBaseline factors Level of dyspnea honeycombing on HRCT Pulmonary hypertension DLCO,40%predicted Desaturation 10%absolute value Decrease in DLCO by 15%absolute value Worsening of fi
26、brosis on HRCTAcute Exacerbation of IPF（AEIPF）Criteria for AEIPF have included an unexplained worsening of dyspnea within 1 month,evidence of hypoxemia as defined by worsened or severely impaired gas exchange,new radiographic alveolar infiltrates,and an absence of an alternative explanation such as
27、infection,pulmonary embolism,pneumothorax,or heart failure.Therapy for IPFIPF Evidence-Based Treatment:Strong recommendation against the use:Corticosteroid mono therapy(very low)Colchicine(very low)秋水仙碱秋水仙碱 Cyclosporine A(very low)环孢霉素环孢霉素 Combined corticosteroid and immune-modulator therapy(low)激素激
28、素+免疫调节剂免疫调节剂 Interferon gamma 1b(high)干扰素干扰素 Bosentan(moderate)波生坦波生坦IPF药物治疗强烈不推荐下列治疗方案强烈不推荐下列治疗方案:单一激素疗法单一激素疗法 秋水仙碱秋水仙碱 环保霉素环保霉素A 激素激素+免疫抑制剂免疫抑制剂 INF gamma 波生坦波生坦IPF药物治疗不主张推荐下列药物不主张推荐下列药物:乙酰半胱氨酸乙酰半胱氨酸+激素激素+免疫抑制剂免疫抑制剂 乙酰半胱氨酸乙酰半胱氨酸 抗凝治疗抗凝治疗 吡啡尼酮乙酰半胱氨酸对乙酰半胱氨酸对IPFIPF的作用的作用 IFIGENIA IFIGENIADemedts et a
29、l.NEJM 2005吡啡尼酮对对FVCFVC的影响的影响 CAPACITY 1CAPACITY 1P=0.005*Rank ANCOVA(PFD 2403 mg/d vs.placebo at Week 72)P.Noble et al,ATS 2009吡啡尼酮对对FVC的影响的影响 CAPACITY 2剂量反应曲线剂量反应曲线Change in%Predicted FVCP.Noble,ATS 2009 吡啡尼酮对无恶化IPF生存的影响-荟萃分析吡吡有效有效 吡吡无效无效 华法令与IPFINF-?与IPFInterpretation We cannot recommend treatmen
30、t with interferon gamma-1b since the drug did not improve survival for patients with idiopathic pulmonary fi brosis,which refutes previous fi ndings from subgroup analyses of survival in studies of patients with mild-to-moderate physiological impairment of pulmonary function.其它治疗 氧疗与对症治疗 康复 肺移植 中医中药
31、Nature History of IPFSarcoidosisPulmonary Sarcoidosis Sarcoidosis is amultisystem disorder of unknownorigin characterized by noncaseating granulomatous inflammation at sites of disease.Lung and intrathoracic lymph nodes most commonly affected结节病的发展进程 肉芽肿性炎症 吸收复发 治疗/观察宿主因素纤维化并不可逆改变CLINICAL FEATURES T
32、he hilar glands and the lungs are the organs most commonly affected in sarcoidosis and intrathoracic involvement is the most frequent accompaniment of sarcoidosis affecting other organs.Age and sex:the highest incidence in the third and fourth decades,with a variable female predominance.Not diagnost
33、ic Pulmonary:cough,expectoration of sputun,breathlessness,hemoptysis Extrathoracic:skin(erythema nodosum),neurological,cardiac,etc Diagnosis by accidentCLINICAL FEATURESLab test Haemopoietic system:increased ESR,anemia,hypercalcimia,increased LDH,increased activity of serum angiotensin-converting en
34、zyme Tuberculin test:negative Kevin test:positive BAL:lymphocytosis(active 28%),increased ratio of CD4/CD8 Biopsy:lymph node or lung Chest X-ray Hilar adenopathy:the right paratracheal,aortopulmonary window and the hilar.Interstitial lung disease:reticulo-nodular/ground-glass,/alveolar opacity,upper
35、 lobe Pleural effusion70%I,II Ocularneurologickidneyheart sarcoidosis Symptomic with II stage or higher Progressive decline in lung function Malignant hypercalcimia Prednisone 30-40mg/qd1-3month tapering to 15mg for 6-9month,tapering with 2.5mg/wk maintainance for 1-2year结节病疗程Judson MA,The treatment of pulmonary sarcoidosis,Respiratory Medicine(2012),doi:10.1016/j.rmed.2012.01.013结节病激素疗程治疗示意图
