chest clinical cases Progressive Dyspnea in anSubmitted byW. Alex Wade MD Appalachian Coal MinerPulmonary FellowSection of Pulmonary and Critical Care Medicine , Department of MedicineWest Virginia University School of MedicineMorgantown, WVJack L. Kinder, MDChairWest Virginia State Occupational Pneumoconiosis BoardCharleston, WVEdward. L. Petsonk MDProfessor of MedicineSection of Pulmonary and Critical Care Medicine, Department of MedicineWest Virginia University School of MedicineMorgantown, WV
History Physical Exam• A 32-year-old male initially presented in 1991 complaining of dyspnea on exertion and a non-productive morning cough for two years.• He was a lifelong nonsmoker and had worked for 15 years as an underground coal miner, transporting coal in a rubber-tired vehicle.• Five years later, he sought reevaluation due to worsening dyspnea and productive cough.• His lungs were clear and the cardiovascular examination was normal. Saturday, January 19, 2013
Lab• The chest radiograph in 1991 was normal (Figure 1.1)• Five years after initial presentation, blood gases at rest on room air showed mild hypoxia (PaO2 73 mm Hg).• The radiograph then demonstrated multiple bilateral small opacities, as shown in Figure 1.2. Saturday, January 19, 2013
cxr(Figure 1.1) Figure 1.2. Saturday, January 19, 2013
Question 1• What is the most likely diagnosis for this patient?• A. Silicosis• B. Asbestosis• C. Lung cancer• D. Coal Workers’ Pneumoconiosis (CWP)• E. Chronic Obstructive Pulmonary Disease (COPD) Saturday, January 19, 2013
DISCUSSION• CWP is an interstitial lung disease that occurs due to the inflammatory reaction to inhaled coal mine dusts.• When lung clearance mechanisms are overwhelmed, numerous black coal macules develop in the lung parenchyma adjacent to the respiratory bronchioles (1).• As CWP progresses, the macules enlarge and develop into fibrotic coal nodules with associated emphysema.• Radiographically, the pathologic changes of CWP manifest as small rounded opacities less than 10 mm in diameter. Historically, the opacities generally have generally appeared after at least 15-20 years of exposure, although there are recent reports of more rapidly progressive disease (2).• The International Labor Office (ILO) has devised a classification system to describe and quantify the changes of pneumoconiosis on chest radiograph (3).• The ILO classification scores the profusion (number of small pneumoconiotic opacities per unit area of lung) from 0 to 3.• Early (category 1) CWP may produce few or no symptoms.• However, dust exposure can also lead to chronic bronchitis (even in the absence of smoking tobacco), which results in cough, sputum production and wheeze. As CWP progresses, dyspnea becomes severe, and affected patients can develop cor pulmonale, respiratory failure and death (4, 5).• Although silicosis can be a more rapidly developing disease which occurs in underground coal miners, the specific mining job of this patient does not involve activities (e.g., drilling or roof bolting) that typically generate exposure to airborne silica.• However, mining of thin coal seams can create silica exposures in general mining activities, as performed by this worker.• Asbestosis typically causes interstitial lung changes that are more pronounced in the lower lung zones, and have a more reticular rather than nodular appearance.• Although both COPD and CWP can cause changes of obstruction and hyperinflation on a chest radiograph, the small nodules seen on this patient’s chest radiograph would not be typical for COPD.• Lung cancer can cause multiple pulmonary nodules, but the time course and clinical picture in this patient are more consistent with CWP. Saturday, January 19, 2013
History Continued:• The patient ceased employment in 1997 due to a back injury, after having worked 21 years in the mines.• He was seen with worsening dyspnea in 2000, at the age of 41.• He denies any other complaints, such as fevers, chills or sputum production.• Pulmonary function tests (PFTs) showed an FEV1 of 58% predicted and an FVC of 74% predicted.• A chest radiograph was taken at that time (Figure 1.3). Saturday, January 19, 2013
(Figure 1.3). (Figure 1.3). Saturday, January 19, 2013
Question 2• What is the most likely diagnosis to explain this patient’s new findings?• A. Multiple Arterio-Venous (AV) Malformations• B. Primary Adenocarcinoma of the Lung• C. Active M. tuberculosis infection• D. Progressive Massive Fibrosis (PMF)• E. Metastatic Cancer from an unknown primary source Saturday, January 19, 2013
DISCUSSION• Both coal and silica dust exposures trigger inflammation of the airways and the interstitium, and pneumoconiosis can continue to progress for years after termination of all dust exposure (1).• This is one reason why primary prevention through dust control is critical.• Inflammatory nodules can coalesce to form PMF (also called complicated pneumoconiosis), which is recognized on the chest radiograph as one or more lesions 10mm in diameter or greater.• After PMF develops, the fibrosis and associated emphysema often progress even without further dust exposure, as was the case with this patient.• Adjacent lung parenchyma is pulled towards the lesions, which most typically occur in the upper lung.• The large airways are distorted as lung volume is lost and lung function may show obstructive and/or restrictive impairments.• An enlarging PMF lesion can be difficult to distinguish from malignancy, particularly if unilateral.• Silica dust exposure is known to increase the risk of primary lung cancer Also, PMF lesions are frequently PET-positive, which can add to the diagnostic confusion (6).• However, the bilateral masses on this nonsmoking patient’s chest radiograph are typical of PMF, and his clinical course makes primary or secondary lung cancer unlikely.• Exposure to silica dusts increases the risk of developing TB and nontuberculous mycobacterial infections (7).• This is likely due to a dysfunction in cellular immunity.• Miners who have inhaled excessive respirable silica and are subsequently exposed to mycobacteria are more likely to develop active disease.• Although mycobacterial disease should be considered in this patient, there is no cavitation and the radiographic appearance is more typical of CWP than TB.• Arteriovenous malformations can present as large masses, typically in the lower lung zones.• They are usually accompanied by feeder vessels that can sometimes be identified on a chest radiograph.• Bilateral upper lung zone lesions, as seen in this case, are not suggestive of AV malformations. 19, 2013 Saturday, January
History Continued:• Over the next four years, the patient’s dyspnea progressively worsened, and he died in 2004 at the age of 45 from respiratory failure secondary to coal workers’ pneumoconiosis with PMF. Saturday, January 19, 2013
Question 3• Which of the following measures is/are likely to be effective in preventing development of PMF among US coal miners?• A. Decreasing the prevalence of smoking and the number of cigarettes smoked• B. Decrease the number of infections with M. tuberculosis among coal miners• C. Decreasing the exposure to inhaled coal mine dust• D. Decrease the work intensity required by miners Saturday, January 19, 2013
DISCUSSION• Advanced CWP, defined as ILO category 2 or greater, is caused by excessive exposure to respirable coal and/or silica dusts, and greatly increases the risk of development of PMF and important physiologic impairment (8).• As part of the Federal Coal Mine Health and Safety Act of 1969, coal mine operators are required to observe a permissible exposure limit (PEL) for respirable dust of 2.0 mg/m3 (9) .• The goal of this dust limit is not only to decrease the overall incidence of CWP, but also to decrease the incidence of advanced CWP to nearly zero, and thus prevent miners from developing PMF.• However, a small proportion of miners have been observed to develop PMF with an underlying profusion category of 1 or 0 and thus PMF was not completely prevented (10).• A number of studies have shown that PMF development is not accelerated by tobacco smoking, nor is it dependent on Mycobacterial infection.• Most operating coal mines are highly mechanized, which generally has reduced work intensity during mine work, but also results in high rates of dust generation. Saturday, January 19, 2013
HRCT-1• 1. Is the disease unilateral or bilateral?• 1. Disease is bilateral.• 2. What is the anatomic location of the linear structures that reach the pleura?• 2. The structures are in part interlobular septa, but may also include some intralobular fibrosis. – Note that these lines extend over more than one lobule. They are referred to as parenchymal or septal bands or long scars.
HRCT-1• Find 2 examples of architectural distortion-- tenting of the pleura--one in each lung.• Find 2 adjacent centrilobular nodules in the left lung.• Find 2 examples of subpleural lines, one in each lung.
• This lung shows many long, thin lines. The long, non- branching ones correspond to parenchymal bands. Most of the lines form polygons, indicating a patchy fibrosis of interlobular septa. In addition, there are subpleural lines that parallel the pleura, probably representing, in part, interlobular septa bordering partially collapsed lobules. A few centrilobular nodules can be seen.• Find and follow a parenchymal band.• Find a subpleural line.• Find two centrilobular nodules.
• This view of an entire section shows several long, thin, parenchymal bands, as well as thickening of the bronchovascular interstitium.• More detail is shown below.• Trichrome stain (collagen is green)
• At higher magnification of the above section, deposition of collagen in a long, thin, parenchymal band can be seen.• The alveolar parenchyma is mostly normal. Centrilobular interstitium is also fibrotic (see below).• Find and follow a long, fibrotic parenchymal band that spans several lobules.
• At higher magnification of the section above, two regions of centrilobular fibrosis can be seen.• Find the two regions of centrilobular fibrosis.• In time, this fibrosis and that in the interlobular septum will radiate in an irregular fashion into the lobule to cause lobular architectural distortion with centrilobular to interlobular septal bridging and lobular shrinkage.
• This entire section (detailed below) shows more advanced interstitial fibrosis with bridging from interlobular septa to bronchovascular interstitium and distortion of the lobule.• Note that the more central lung parenchyma is spared.• (Trichrome stain for connective tissue)
• This H&E-stained section shows the result of prolonged subpleural, interlobular septal, and centrilobular fibrosis. The fibrosis has distorted the lobular architecture and linked centrilobular and interlobular septal structures. Inflammatory cells are sparse.• Find an example of a bronchiolovascular bundle.• Note how it is connected to a thickened interlobular septum to its left.• Find a portion of an interlobular septum with a vein cut longitudinally.• Note areas of subpleural fibrosis.• The radiating fibrosis in the right lower quadrant (outline it) represents linked lobular and interlobular septal fibrosis.
• Here, peribronchiolar fibrosis, which represents a centrilobular nodule on HRCT, is present. Nearby peribronchiolar air spaces have been obliterated, but more distal ones are intact.• Find the bronchiolar lumen.• Find the pulmonary artery.• Find 2 collections of brown pigment in air spaces.• What does the pigment represent?• Collections of hemosiderin pigment.
• In this lung, note the marked thickening of the visceral pleura.• Find where the pleura has folded into the lung parenchyma.• Find the curved deviation of the interlobar fissure caused by the scar.• Find the mild deviation of 2 large vessels toward the pleural infolding.• In HRCT image 1 above, the architectural distortion in the anterior right lung is an example of this pleural infolding.• Note that there is no honeycombing (see below) in this lung.
• This is an example of a lung with more advanced disease.• Note pleural thickening at the base.• The normally smooth, lateral pleural margin shows architectural distortion, which is caused by irregular, subpleural fibrosis (causing subpleural nodules on HRCT).• Find a small subpleural scar (subpleural nodule)• Compare the abnormal parenchyma in the upper lateral, subpleural region to the more normal parenchyma medially. What is the abnormality?• Honeycombing, consisting of small cystic spaces with thick walls (more on honeycombing later).
What is it• The cause of the changes noted above is shown here. What is it?• This is an asbestos body, which is a thin asbestos fiber that has been coated with an iron-protein coat within a macrophage.• The asbestos body is often found in areas of hemosiderin pigment.
Differential diagnosis• Differential diagnosis of parenchymal bands with architectural distortion on HRCT: – Asbestos-related lung disease, – Atelectasis. – Tuberculosis. – Sarcoidosis. – diffuse pulmonary fibrosis.
Histologic differential diagnosis:• Histologic differential diagnosis:• The presence of asbestos bodies and a history of asbestos exposure distinguish this entity from other fibrosing diseases such as: – usual interstitial pneumonia. – and fibrosis caused by a drug. – organic and other inorganic dusts. – radiation, or collagen vascular diseases.
Diagnostic features of asbestosis on HRCT:• Diagnostic features of asbestosis on HRCT: In a person with a history of asbestos exposure, the diagnosis of asbestosis can be based on the HRCT if three or more of the following abnormalities are present :• Interlobular septal thickening and centrilobular nodules.• Parenchymal bands.• Architectural distortion of the lobule.• Honeycombing.• Subpleural lines.
Q1• Regarding respiratory surfactant:• A- It is produced by alveolar type 2 epithelial cells.• B- It is composed primarily of phospolipids such as dipalmitoyilelecithin.• C- It reduces lung compliance by changing surface tension.• D- Production may be enhanced by the administration of antenatal steroids to mother.• E- At 24 weeks gestation, production is 75% of that at term. Saturday, January 19, 2013
A1• Regarding respiratory surfactant:• A- It is produced by alveolar type 2 epithelial cells. (True)• B- It is composed primarily of phospolipids such as dipalmitoyilelecithin. (True)• C- It reduces lung compliance by changing surface tension. (False)• D- Production may be enhanced by the administration of antenatal steroids to mother. (True)• E- At 24 weeks gestation, production is 75% of that at term. (False) Saturday, January 19, 2013
Q2• The following syndromes are associated with respiratory tract abnormalities:• A- CHARGE Syndrome• B- Ciliary dyskinesia• C- Hurlers Syndrome• D- Tay Sachs Disease• E- Cri-du-Chat Syndrome Saturday, January 19, 2013
A2• The following syndromes are associated with respiratory tract abnormalities:• A- CHARGE Syndrome(True)• B- Ciliary dyskinesia(True)• C- Hurlers Syndrome(False)• D- Tay Sachs Disease(False)• E- Cri-du-Chat Syndrome(True) Saturday, January 19, 2013
Q3• Characteristic features of idiopathic diffuse interstitial fibrosis of the lung (HAMMAN- RICH) include:• A- Cyanosis on exercise .• B- Inspiratory crackles on auscultation .• C- Hypercapnia .• D- Decreased FEV1/FVC ratio .• E- Decreased gas transfer factor Saturday, January 19, 2013
A3• Characteristic features of idiopathic diffuse interstitial fibrosis of the lung (HAMMAN- RICH) include:• A- Cyanosis on exercise . (True)• B- Inspiratory crackles on auscultation . (True)• C- Hypercapnia . (False)• D- Decreased FEV1/FVC ratio . (False)• E- Decreased gas transfer factor(True) Saturday, January 19, 2013
Q4• The following conditions are associated with sleep apnoea:• A- Anorexia nervosa .• B- Large uninflammed tonsils .• C- Guillain-Barre Syndrome .• D- Ondines Curse .• E- Diencephalic Syndrome Saturday, January 19, 2013
A4• The following conditions are associated with sleep apnoea:• A- Anorexia nervosa . (False)• B- Large uninflammed tonsils . (True)• C- Guillain-Barre Syndrome . (True)• D- Ondines Curse . (True)• E- Diencephalic Syndrome(False) Saturday, January 19, 2013
Q5• A 7 year old girl presents with acute cough and wheeze, and is given nebulised salbutamol. The following are indications for admission to hospital:• A- A peak flow rate of 80% of that predicted for height.• B- Continuing cough.• C- Respiratory rate of 40/min.• D- Saturation of 90% in air.• E- She looks tired. Saturday, January 19, 2013
A5• A 7 year old girl presents with acute cough and wheeze, and is given nebulised salbutamol. The following are indications for admission to hospital:• A- A peak flow rate of 80% of that predicted for height. (False)• B- Continuing cough. (False)• C- Respiratory rate of 40/min. (False)• D- Saturation of 90% in air. (True)• E- She looks tired. (True) Saturday, January 19, 2013
Q6• Chest signs that are reliable diagnostically are found in:• A- A neonate with meconium aspiration.• B- A 3 month old child following aspiration pneumonia.• C- A 4 month old child with bronchiolitis.• D- A 6 month old with lobar pneumonia.• E- A 2 year old with inhaled foreign body. Saturday, January 19, 2013
A6• Chest signs that are reliable diagnostically are found in:• A- A neonate with meconium aspiration. (False)• B- A 3 month old child following aspiration pneumonia. (False)• C- A 4 month old child with bronchiolitis. (True)• D- A 6 month old with lobar pneumonia. (False)• E- A 2 year old with inhaled foreign body. (False) Saturday, January 19, 2013
Q7• In the normal adolescent lung:• A- There is an intrapleural pressure of 30cmH2O (3kPa) at the end of normal expiration.• B- There is a resting pulmonary blood flow of 10L/min.• C- The V:Q ratio is greater in apical than basal segments of the lung when upright and at rest.• D- The majority of airway resistance is from large airways.• E- Cartilage is present in all respiratory bronchioles. Saturday, January 19, 2013
A7• In the normal adolescent lung:• A- There is an intrapleural pressure of 30cmH2O (3kPa) at the end of normal expiration. (False)• B- There is a resting pulmonary blood flow of 10L/min. (False)• C- The V:Q ratio is greater in apical than basal segments of the lung when upright and at rest. (True)• D- The majority of airway resistance is from large airways. (False)• E- Cartilage is present in all respiratory bronchioles. (False) Saturday, January 19, 2013