Interstitial Lung Disease ILD

General description



ILDs represent a large and heterogeneous group of lower respiratory tract disorders.



There are similar clinical signs and X-ray features

.

The characteristic of clinical signs including:



Dyspnea after exercising



chest X-ray shows diffuse abnormality of pulmonary parenchymal,including nodules,linear(reticular) infiltrates



pulmonary function tests shows restrictive hypoventilation reduced diffusing capacity



tissue biopsy shows a variety pulmonary fibrosis and aveolar inflammation

Clinical Classification of ILD



known cause



unknown cause (IIP,ects)

Pathogenesis

 The pathogenesis of ILDs is unknown.

 But more and more facts have shown that immune cells and their cytokines play an important role in the course of ILDs.

Nowadays the major courses of the ILDs including:

 Intra-alveolar inflammation  immune cells and their cytokines injure epithelial and endothelial cells  intra-alveolar fibrosis/alveolar collapse

In the course of ILDs, many cytokines, including TGF  , IGF  , prostaglandin E 2 , platelet derived growth factor, ects, involve in.

Clinical manifestations

 Breathlessness, Progressive respiratory insufficency  cough without sputum.  Some patients may have fatigue, weight loss, joint pain.

Physical examinations

 Bilateral basilar, crepitant velcro-like rale are found in most patients  wheezing, rhonchi and coarse rales are occasionally heard  with advanced disease, patients may have tachypnea and tachycardia  clubbing of the fingers and toes is common  At last, pulmonary hypertention and cor pulmonale may be exist

Chest radiography

It is important method to diagnose the ILDs. The majority of ILDs cause infiltrates in the lower lung zones.

 A diffuse ground glass pattern is seen early in the disease  when the disease progresses, a chest radiography demonstrates nodules, linear(reticular) infiltrates, or a combination of the two  at last, the infiltrates become coarser and lung volume is lost  honeycomb pattern may appear at the end of the disease

nodular linear

nodular linear

honeycomb

ground glass pattern

Pulmonary function tests

Pulmonary function tests of ILDs shows restrictive hypoventilation.

It includes:

 Reduced lung volumes(vital capacity, total lung capacity)  reduced diffusing capacity  static lung compliance is decreased

BALF examination

 the cell counts in BALF of ILDs is twice than that of normal humans  cell complements of ILDs is difference from that of normal humans  for example, the percents of neutriphils in BALF of IPF is higher than that of normal humans

Blood examination

Lung biopsy

For example, TBLB(transbronchial biopsy), an open-lung or thoracoscopic biopsy are used to diagnose the ILDs

Idiopathic pulmonary fibrosis IPF

 IPF is an

unknown

chronic interstitial lung disease.Nowadays It has become a common disease.

 the clinical manifestations, and some experimental examination including pulmonary function tests,chest radiography examinations and lung biopsy are coincide to that of ILDs introduced before.

Pathology: According to the pathologic classification, there are seven types of

Idiopathic

pneumonitis.

interstitial



IPF-UIP(usual interstitial pneumonitis)



NSIP, nonspecific interstitial pneumonitis



DIP, desquamative interstitial pneumonitis



RBILD, respiratory brnchiolitis associated interstitial lung disease



LIP, lymphocytic interstitial pneumonitis



COP, concealed organizing pneumonia



AIP, acute interstitial pneumonitis

How to diagnose IPF



According to the clinical signs and some experimental examinations, we can diagnose the IPF except some known cause ILDs



lung biopsy is an only way to give a last diagnosis

Clinical Diagnostic Standard of IPF



Except known cause ILDS



Lung function



HRCT



TBLB and BAL



Age



Unexplained dyspnea after exercise



Period



Physical examination

Chest radiography

Chest radiography

Pathologic Diagnosis



The pathologic diagnosis of IPF is coincide with UIP

Treatment of IPF



Nowadays, the treatment ways of IPF are lack of effective ways



corticosteroids are the main therapy



the initial treatment of choice is prednisone 0.5mg/kg of ideal body weight per day. For 1 month, the dose is gradually tapered over several months to a maintenance dose of 0.125 mg/kg per day



Immunosuppressive agents,including CTX, MTX



lung transplantation

Treatment

 Some common therapies, including oxygen therapy, antibiotic therapy when pulmonary infections exist.

prognosis

Sarcoidosis

Definition



Sarcoidosis is a disease of unknown cause and is characterized by the presence of

non caseating granulomas

in one or more organ, system. It is considered

a systemic disease



Usually lungs and the lymph nodes in the mediastinum and hilar regions are the most site of involvement



The clinical course is

quite variable

asymptomatic

The cause of sarcoidosis is

unknown

. But many researchers have suggested that immune mechanisms are important in disease pathogenesis.Genetic factor may also play an important role.

Other factors including infectious and environmental or occupational may also involve in the sarcoidosis.

Pathogenesis



Antigen processing by macrophages is believed to trigger an oligoclonal expansion of CD4(helper-inducer) lymphocytes of the Th1 phenotype with production of IL-2 and IFN-



.



IL-2 cause proliferation of more CD4 cells, elaborate more cytokines.



Many cytokines, mainly IL-2,adhension molecules and growth factors are released from lymphocyte and macrophages.

The basic pathogenesis includes three main stages:



Pulmonary alveolus inflammation



formation of non-caseating granulomas



the stage of interstitial fibrosis

Clinical manifestations



The clinical course is variable



the respiratory system is the most commonly affected



approximately 90% of patients demonstrate intrathoracic involvement on a chest radiograph



sometime with or without extrathoracic disease

Clinical manifestations



Almost 30 to 60 per cent of patients have no symptoms at the time of presentation



sometimes the disease is identified because of abnormalities on a chest radiograph



some patients present with respiratory symptoms such as dyspnea and cough, which may or may not be accompanied by constitutional symptoms, such as fever and malaise

Specific signs and symptoms depend on the particular organ system(s) involved



Respiratory system disease



Intrathoracic nodal involvement and parenchymal lung disease are the most common ways in which sarcoidosis affeccts the respiratory system



Hilar and medistinal lymph nodes may be affected



The pulmonary parenchyma demonstrates well defined,non-caseating granulomas with the pulmonary interstitium



Usually upper lobes of the lung tend to be more involved

Extrapulmonary sarcoidosis

Including:



skin disease: about 20-25% of patients are involved lesions include papules, plaques, nodules and lupus pernio, erythema nodosum



eye disease and neurologic disease, liver and spleen, peripheral lymph nodes, bone lesions and myopathy

Experimental examinations and some specific examinations



elevations in the level of angiotensin converting enzyme(ACE) (the normal level is 17.6-34u/ml). The measurement of serum ACE might be a useful diagnostic and prognostic test in sarcoidosis



hypercalcemia: a potentially important complication of sarcoidosis



PPD test: about 2/3 patients with sarcoidosis has no reaction



Kveim antigen test: we can’t usually used the test we have not standard antigen



bronchial-alveolar lavage fluid examination(BALF): the lymphocyte percent of the BALF is elevated. Usually, the percent of lymphocyte of BALF is more than 28%.It demonstrates that the disease is active



tissue biopsy:



an affected organ or tissue are generally used to diagnostic biopsy, including skin, lymphy node,ects.



Flexible electric bronchoscopy with transbronchial lung biopsy(TBLB)



Mediastinoscopy is sometimes performed in the presence of isolated mediastinal adenopathy

X-ray examination



The plain chest radiography is an important way to diagnose sarcoidosis.



The major abnormalities seen on the chest radiograph include: lymphadenopathy,usually involving both hila and mediastinal,and involvement of the pulmonary parenchyma



Computed tomography(CT) of the chest is used to evaluate of suspected sarcoidosis, especially there is need for better definition of mediastinal lymph node involvement.



High-resolution CT is used to demonstrate that pulmonary parenchymal involvement is localized around bronchovascular structures, producing an appearance resembling budding branches on a tree.



Usually, The features of HRCT of patient with sarcoidosis shows numerous small nodular in a predominantly bronchovascular distribution

Scanning with gallium citrate-67 is a more sensitive method to evaluate the activity of sarcoidosis

Diagnosis and differential diagnosis



According to the clinical signs, chest X-ray, tissue biopsy, we can diagnose the sarcoidosis.



Nowadays the standard to diagnose the sarcoidosis includes:



chest X-ray shows that bilateral hilar and mediastinal adenopathy, accompany with(or without) small nodules in pulmonary parenchymal



Tissue biopsy shows that characteristic of affected organ and tissue is conincide to sarcoidosis



The Kveim test is positive



The PPD test is negative or weak positive



Hypercalcemia and hypercalciuia



The lymphocytes of BALF is elevated



The level of SACE is elevated



Among them, the first and the second are more important. If a patient has both the first one and the second one, we can diagnose

Differential diagnosis including



The tuberculosis of hilar lymphy node. Usually, the patient with tuberculosis may have clinical signs of tuberculosis.PPD test is positive. Biopsy shoud be done if we couldn’t diagnose

Differential diagnosis including



lymphoma.Usually we must do biopsy



The transferred tumor of hilar:the patient with transferred hilar adenopathy usually shows the clinical signs caused by primary tumor. For example, the chest X-ray of patient with lung cancer sometimes shows not only pulmonary parenchymal involvement but also hilar and mediastinal adenopathy



Treatment

Most of patients, especially those with no clinical signs need no therapy.



If patients with clinical signs, the need to therapy. For example, parenchymal lung disease is a potential indication, depending on its effects on pulmonary function and symptoms, not on the severity of radiographic involvement.Nowadays corticosteroids are also a major treatment method. They can alter its long-term natural history, improve the clinical signs promptly, prevent progressive pulmonary fibrosis



Usually prednisone is started at 40mg/d.The dose can be tapered with the good of using lowest dose that keeps the disease under adequate control.



Treatment durations usually is one year



Another drugs, including cytotoxic agents(for example methotrexate), hydroxychloroquine

Prognosis

Table 1 Radiographic staging of intrathoracic sarcoidosis stage hilar adenopathy parenchymal disease 0 No No 1 Yes No (both hilar and mediastinal right paratrachcal) 2 yes yes (usually shows small nodules interstitial fibrosis) 3(or 4) No yes (with fibrosis

)

 1.

间质性肺病的肺功能特点为 :A  A.

限制性通气障碍为主 , 弥散功能下降  B 阻塞性通气障碍为主 , 弥散功能下降  C 限制性通气障碍为主 , 弥散功能正常  D 阻塞性通气障碍为主 , 弥散功能正常  E 限制性通气障碍为主 , 弥散功能正常

 2.

诊断间质性肺病的金标准是 :E  A 肺功能  B 临床表现  C 肺 HRCT  D 支气管镜检查  E 肺活检病理

 3.

目前 IPF 最主要的治疗药物是 :C  A 抗菌素  B 支气管扩张剂  C 糖皮质激素  D 止咳化痰药  E 呼吸兴奋剂

 4.

结节病的基本病理改变为 :B  A 干酪样肉芽肿性病变  B 非干酪样肉芽肿性病变  C 纤维化样改变  D 以嗜酸性粒细胞浸润为主的炎症  E 以中性粒细胞浸润为主的炎症

 5.

结节病患者的支气管肺泡灌洗液细胞成 分分析中以何种细胞为主 C  A 中性粒细胞  B 嗜酸性粒细胞  C 淋巴细胞  D 嗜碱性粒细胞  E 肥大细胞

 6.

下列哪项不符合弥漫性间质性肺疾病的 表现？ E  A 、干咳  B 、气急  C 、杵状指  D 、 X 线胸片呈弥漫性炎变  E 、肺功能呈阻塞性通气功能障碍

      7 ． 24 岁，一周来低热，乏力，胸痛，气促，体检：右 胸叩诊实音，呼吸音消失，胸水常规草黄色，比 重 1.030

， WBC ： 0.8

＊ 10^9/L ，淋巴占 LDH ： 300u/dl ，胸水 LDH/ 血清 80 ％，蛋白 34g/L ， LDH 比值为： 0.75

， 最可能的诊断是： E A 、右侧肺炎伴胸水 B 、肺癌伴胸膜转移 C 、肝硬化伴胸水 D 、慢性肾功能不全伴胸水 E 、结核性胸膜炎

      8 ． 24 岁，一周来低热，乏力，胸痛，气促，体检：右 胸叩诊实音，呼吸音消失，胸水常规草黄色，比 重 1.030

， WBC ： 0.8

＊ 10^9/L ，淋巴占 LDH ： 300u/dl ，胸水 LDH/ 血清 80 ％，蛋白 34g/L ， LDH 比值为： 0.75

， 最可能的诊断是： E A 、右侧肺炎伴胸水 B 、肺癌伴胸膜转移 C 、肝硬化伴胸水 D 、慢性肾功能不全伴胸水 E 、结核性胸膜炎

      9 ． 45 岁男性， 影，血气分析： 1 年前不明原因活动后气促，逐渐加重， 体检：轻度发绀，肺底部少量细湿罗音，有杵状 指， 胸片示双肺中下野肺纹理增多呈网状，并有结节状阴 PaO2:60mmHg ， PaCO2:35mmHg ， 以 下哪项诊断可能性最大？ D A 、慢性支气管炎 B 、支气管哮喘 C 、支气管扩张 D 、弥漫性肺间质纤维化 E 、支气管肺癌