1、Restrictive and Obstructive Diseases -Pulmonary Pathology Lab 3-,Robert Allan, MD,Restrictive and Obstructive Lung Pathology- Background,What is the fundamental problem in restrictive lung disease?,You cant get air in the lungs,What is the fundamental problem in obstructive lung disease?,You cant ge
2、t air out of the lungs,Name two major disease categories that are obstructive lung diseases?,Chronic obstructive pulmonary disease (COPD) which includes emphysema and chronic bronchitis Asthma,Restrictive and Obstructive Lung Pathology- Background,What happens to the total lung capacity (TLC) in res
3、trictive lung disease?,It goes down. You have less total lung capacity. You cant get air in.,What happens to the total lung capacity (TLC) in obstructive disease?,The total lung capacity (TLC) in obstructive lung diseases is INCREASED. The reason this happens is that patients with obstructive diseas
4、es trap air in their lungs (they cant get air out) and as a result the TLC in their lungs is actually increased.In order to measure the lung function pulmonologists do something called spirometry (hopefully you covered this in physiology). In simplified terms you measure the amount that the person c
5、an puff out at 1 second (Forced expiratory volume-1, FEV1) compared to the total amount they can puff out (Forced vital capacity- FVC).This is often expressed as the ratio of FEV1/ FVC.,Restrictive and Obstructive Lung Pathology- Background,What do you think happens to the FEV1/FVC ratio in obstruct
6、ive lung diseases, in restrictive lung disease? (yes I know this wasnt in lecture if you can figure this out yourself you will remember it),In OBSTRUCTIVE disease (remember cant get air out)- the amount that you can get out of your lungs at one second will be diminished. As a result the proportion o
7、f the amount you can breath out at one second will be diminished relative to the total amount that you can breath out (forced vital capacity). The FEV1/FVC will be reduced (normal around 0.8). One confusing point is that patients with obstructive disease often have diminished FVC. This is due to the
8、 fact that despite their best efforts (increasing their TLC) they still have air trapped in their lungs and therefore the amount that they can actually get out of their lungs (FVC) is diminished.In RESTRICTIVE disease (remember cant get air IN)- you couldnt get the air in the lungs in the first plac
9、e. This should not alter the ratio of the amount you can exhale in one second so the FEV1/FVC should stay the same. Remember the total amount that you can exhale (FVC) will be diminished (because you couldnt get the air in in the first place)- but there is no reason the relative amount you can exhal
10、e at 1 second should be diminished compared to normal (FEV1/FVC ratio is the same). Actually in some instances if the reduction in FVC is significant the FEV1/FVC can actually be increased relative to normal!,Restrictive and Obstructive Lung Pathology- Background,Forced expiratory ratio (FEV1/FVC ra
11、tio of FEV1%)- Shown graphically (dashed green is normal, black abnormal),Restrictive ventilatory pattern,Obstructive ventilatory pattern,FVC slightly reduced FEV1 reduced FEV1/FVC ratio reduced,FVC reduced FEV1 reduced FEV1/FVC ratio normal,Patterns of Abnormal Function for Various Pulmonary Disord
12、ers,Here is a summary table that is a bit simplified. To reiterate in obstructive diseases air cannot get out. This leads to a prolonged expiratory phase and decreased FEV1. If the obstruction is bad enough these folks may actually trap air in their lungs that they cannot get out at the end of expir
13、ation- this leads to a lower FVC but higher TLC (they are all puffed up but the air isnt getting out hence the FVC is a little bit lower)In restrictive the air never got in. The FVC is going to be low- generally much lower than the diminished FVC in patients with obstructive pattern. They are not ob
14、structed so the ratio of FEV1/FVC is going to be normal or even increased (they have so little air in the lungs that they can get most of it out at one second- more than a healthy person),Case 1-,A 54 year old coffee salesman present with a two week history of increasing cough and shortness of breat
15、h. He has no significant past medical history other than mild obesity, hypertension. He is afebrile. He has no sick contacts or exposures. His work involves selling whole bean fair trade organic coffee- he is not exposed to any organic material or chemicals. He does not have pets or exposure to bird
16、s.Chest x-ray and CT were performed. There was no dense infiltrate. The CT scan shows patchy, peribronchial areas of infiltrates. Spirometry was performed. The tracing is shown. Green is normal. Black is the patient.How would you characterize this process?,This shows a restrictive pattern.,Case 1-,W
17、hat would you consider in your differential diagnosis among the entities discussed with this pattern on spirometry?,The differential would include entities with a restrictive pattern on spirometry. Infection would be considered in the differential though the pattern on spirometry can vary so it will
18、 not be discussed here for example if the infection is chronic bronchitis it can have an obstructive pattern, if it is more distal it can have a restrictive pattern or mixed features.So among restrictive diseases discussed: Sarcoidosis this could be included in the differential despite the absence o
19、f hilar lymphadenopathy Hypersensitivity pneumonitis the absence of any compelling exposures would argue against it however, more investigation and clinical history may be helpful Pneumoconiosis or UIP would be excluded by the absence of exposures or radiographic findings typical for these disorders
20、 Collagen vascular disease- not likely given absence of history Cryptogenic organizing pneumonia- this is possible if all other possibilities are excluded.,Case 1- The coughing coffee trader,A comprehensive infectious disease work-up is negative. There is no evidence by laboratory studies of a colla
21、gen vascular disease. The third year medical student on the service spent two hours getting a comprehensive exposure history and none was detected.A lung biopsy was performed. This is shown on the next slide.,Case 1- The coughing coffee trader,What would be the most reasonable diagnosis in this case
22、?,Cryptogenic organizing pneumonia. This is truly idiopathic (unknown etiology so this diagnosis is appropriate),Case 1- The coughing coffee trader,What is the feature circled that helped make the diagnosis?,Loose fibroconnective tissue plugs (Masson bodies),Case 2-,A 59 year old female presents wit
23、h a two year history of progressive shortness of breath, cough, weight loss and fatigue. She has no significant medical history. She is a lifelong non-smoker. She has no exposures, she does not have pets or is not exposed to chemicals. Lung function tests were performed. Green is normal. Black is th
24、e patient.How would you characterize this lung function test?,This shows a restrictive pattern.Understand what the axis and graph means so that if someone flips the X and Y it will still make sense. Even without the numbers, this pattern shows you that the total forced vital capacity is low compared
25、 to normal (green) but the FEV1/FVC will be normal.,Case 2- Progressive shortness of breath,A chest CT scan was performed. This image is from the lung base. You get to play radiologist what problem to you see?,Without going into too much detail- the most important finding is the presence of honeycom
26、bing, the cystic spaces shown by the arrow that are accentuated in the lower lobes as show in this CT scan. This is not emphysema because there is also an increase in fibrosis in the interstium.,Case 2- Progressive shortness of breath,An open lung biopsy was performed. You get to play pathologist wh
27、at is your diagnosis?,Case 3-,A 33 year old female presents with a two week history of shortness of breath, cough, mild fever. Her symptoms started the day after she decided to clean out her basement which was “an unbelievable mess” which contained bird droppings, feathers, mold, mushrooms, dust and
28、 old notes from her boyfriends systemic pathology course which he said he was intending to burn as soon as the course was over but never got around to it. The symptoms improved when she went to work but started up again and maybe were a bit worse when she went down to clean out the basement again. S
29、he has no significant past medical history other than mild asthma. She tells you that she must be “allergic” to something in the basement. Lung function studies were performed. Green-normal, Black- patientHow would you characterize this lung function test?,This shows a mild restrictive pattern. She
30、grabs the result of the spirometry and states that this must be related to her asthma. What should you tell her, is this related to her asthma?,Volume (L),Time (seconds),1,This pattern would not be expected for asthma which would show an obstructive pattern.,Case 3- Cough with a cleaner basement,Giv
31、en the results of the spirometry a lung CT scan was performed which shows diffuse small nodules and ground glass opacities. The radiologist says that the pattern reminds her of something called “extrinsic allergic” or something like that.What other pertinent negative would be important (tough questi
32、on)?,- This is a tough question. In general I was getting at the main differential of hypersensitivity vs. sarcoidosis in which it would be important to know if there is hilar/ mediastinal lymphadenopathy. There is no lymphadenopathy in this case. Not all cases of sarcoid have mediastinal lymphadeno
33、pathy- however it is unusual for hypersensitivity to have enlarged hilar or mediastinal lymph nodes,Case 3- Cough with a cleaner basement,A virtual open lung biopsy was performed. The findings are shown below. The arrowheads show poorly formed granulomata. What is the most likely diagnosis?,- The bi
34、opsy shows an increase in interstitial chronic inflammation, poorly formed granulomata(left) and other areas showed a bronchiolitis obliterans organizing pneumonia (BOOP) pattern. I used the exact same picture as before to highlight the non-specific nature of the BOOP pathologic pattern. This is mos
35、t likely hypersensitivity pneumonitis,Case 3- Cough with a cleaner basement,You tell her that she has hypersensitivity pneumonitis and that she should avoid cleaning out the basement. She tells you that she thought it was her asthma all along and that this was an allergic reaction. Is she correct?,N
36、o. Despite the rather unfortunate name “extrinsic allergic alveolitis”- the pathogenesis of this disorder has nothing to do with “allergies” or type I hypersensitivity reactions or asthma. The pathogenesis is thought to be due to a type III or type IV delayed type “hypersensitivity” reaction.Lets as
37、sume that she ignores your advice and decides that her passion in life is to clean basements no matter how much it makes her cough or get short of breath . She continues doing this for many years and when she is 55 years old sees you again. A chest CT scan was performed and the radiologist tells you
38、 that there is honeycomb change and an increase in interstitial fibrosis and writes in her report changes consistent with “idiopathic pulmonary fibrosis (IPF)”. How could this be?,- The patient has a usual interstitial pneumonia pattern that is due to chronic hypersensitivity pneumonitis. Remember t
39、hat the UIP pattern may be seen in many of the interstitial lung diseases. The radiologist wrote “IPF” because she likely did not have any history and/or assumed it was idiopathic.,Case 3-,A 33 year old African American female presents with nagging cough. She has no other significant history. She de
40、nies any exposures to pets, occupational exposures or history of asthma. Lung function studies were performed which showed a mild restrictive pattern. Green-normal.Which color line would correspond to a mild restrictive pattern?,Volume (L),Time (seconds),1,Red line- Mild restrictive pattern Orange l
41、ine- Crazy pattern incorrect answer Blue- Severe restrictive defect (close) Purple- Obstructive pattern,Case 3- Nagging cough with big lymph nodes,Chest x-ray is remarkable for the presence of enlarged hilar and mediastinal lymph nodes. CT scan of the chest shows a nodular infiltrate that runs along
42、 the airways and lymphatics.What is the biggest clue to the diagnosis ?,- The biggest clue is the presence of enlarged lymph nodes. The pattern of the nodular infiltrate in the lungs around airways and lymphatics is also a clue,Case 3- Nagging cough with big lymph nodes,A transbronchial biopsy is pe
43、rformed. The clinical history is hard to read and it is transcribed as “rule out Sarcoma(?), rule out lymphoma, rule out infection”. The biopsy is shown below. What is the most likely diagnosis and what additional studies need to be performed?,- The most likely diagnosis is sarcoidosis. This is base
44、d on the presence of well formed, non-caseating granulomata that are easily identified in the biopsy. Stains for mycobacteria (AFB stain) and fungi (GMS stain/ silver stain) need to be performed to help exclude an infectious cause for the granulomas inflammation.,Case 3- Nagging cough with big lymph
45、 nodes,Both sarcoidosis and hypersensitivity pneumonitis can give you a restrictive lung pattern, infiltrates and granulomas on biopsy. Which one of the two has well-formed non-necrotizing granulomata?,SarcoidosisWhich one has granulomata that are airway and perilymphatic in distribution?,Sarcoidosi
46、s.Which one typically has more chronic inflammatory cells and may have areas of BOOP pattern?,Hypersensitivity pneumonitisWhich one is cause by a type I allergic hypersensitivity reaction?,Neither.,Case 4-,A 13 year old female presents with a two year history of multiple bouts of difficulty breathin
47、g, wheezing and coughing. Each time the symptoms seem to go away but this time they are worse and persistent and she wants to feel better. She has no history of any medical disorders, exposures or sick contacts. Lung function studies are performed. Green-normal, Black- patientHow would you character
48、ize this lung function test?,This shows an obstructive pattern. The ratio of the FEV-1/ FVC is lower than normal. Here the patient (black) line cannot force out as much air as a normal person at 1 second. She cannot get all of the air out and so her FVC is diminished but not too diminished. This res
49、ults in a lower FEV1/ FVC ratio compared to normal.,Volume (L),Time (seconds),1,Case 4- Wheezer,You administer a bronchodilator. Within 30 minutes she feels that her breathing improves. The spirometry shows an improvement in the obstructive pattern. The black line is the patients spirometry result a
50、t admission. Which colored line shows an improvement in the obstructive pattern?,ORANGE- Shows an improvement in the obstructive pattern compared to the black line at admission.,Volume (L),Time (seconds),1,Case 5- Short of breath smoker,A 58 year old male presents with significant dyspnea. He has a
51、significant smoking history- he started when he was 13 and has smoked about 1-2 packs per day since that time. He does not have significant sputum production. On physical examination he is slender and breathes with pursed lips on exhalation. He cannot walk up a flight of stairs without getting significantly out of breath. Spirometry was performed. Green-normal, Black- patientHow would you characterize this lung function test?,
