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[Dr. Handy] Hi, welcome to Harrison's Podclass where we discuss important concepts in internal medicine. I'm Cathy Handy. [Dr. Wiener] And I'm Charlie Wiener, and we're coming to you from the Johns Hopkins School of Medicine. [Dr. Handy] Welcome to episode 70, a 48-year-old with worsening cough. [Dr. Wiener] Hi Cathy, so the question begins today, a 48-year-old man presents with worsening cough and exertional dyspnea over the past two months.
He currently smokes one and a half packs of cigarettes per day, and he's done so for 30 years. [Dr. Handy] So he started early and has smoked a lot. It's a heavy smoking history. [Dr. Wiener] Yeah, he attains PFTs and they show a normal ratio of FEV1 to FVC, a total lung capacity that is 75% of predicted, and diffusing capacity that is 60% predicted. What do you think of those results? [Dr. Handy] Well, we'll talk about those in a minute but how about a physical examination?
That would be helpful in this case. - [Dr. Wiener] How so? - [Dr. Handy] Well, in a smoker with cough, I'm definitely interested in oxygen saturation and JVP looking for hypoxemia and any signs of right heart dysfunction. [Dr. Wiener] What about the lung exam? Are you going to include that? [Dr. Handy] Absolutely, I'd want to look for a prolonged expiratory phase, expiratory wheezes, and inspiratory crackles because all of those could be helpful in understanding what's going on.
[Dr. Wiener] All right, well, I'll give you that in a minute, but what do you think of his PFTs? [Dr. Handy] All right, well first off with his normal FEV1 to FVC ratio he does not have an obstructive ventilatory defect, and therefore I'm less suspicious that COPD will explain his symptoms.
But I will note that his TLC is less than 80% predictive, indicating a mild restrictive ventilatory defect and his diffusing capacity or DLCO is 60% predicted, indicating that he does have a moderate gas transfer defect. [Dr. Wiener] And where are those going to lead you? You already said, away from COPD. [Dr. Handy] Well, a restricted ventilatory defect with a normal DLCO would make me think of neuromuscular diseases, so on that list would be ALS or chest wall diseases, like kyphoscoliosis.
His DLCO is actually more reduced than his TLC, and that makes me think that he may have an interstitial lung disease. A CT is often times helpful in this case. [Dr. Wiener] All right, and you wanted a physical exam and I promised I'd give you that. So his resting oxygen saturation is 91% on room air, his jugular venous pressure is normal, his cardiac exam is normal.
You do hear inspiratory fine crackles on both sides, bilaterally, and there's a little bit of a basal predominance but nothing else. He has no peripheral edema or any other signs suggesting cardiac failure. [Dr. Handy] And the CT scan? [Dr. Wiener] A high resolution CT scan of the chest shows diffuse centrilobular nodules, and scattered ground-glass opacities. There's no emphysema, the pulmonary arteries and the right heart appear normal. There is no evidence of any emphysema.
Sound like interstitial lung disease to you? [Dr. Handy] Yeah, it does and like you mentioned already, too we've sort of ruled out a lot of heart disease as a potential cause of his symptoms. [Dr. Wiener] Okay, how do you think of the interstitial lung disease? They have a bunch of confusing acronyms. [Dr. Handy] Yeah, there are some known causes so for example, based on exposures associated with systemic diseases, again a more thorough history and physical will help with those.
[Dr. Wiener] What are some of the examples in those categories? [Dr. Handy] Well, occupational exposures would include asbestosis or silicosis, some therapies, such as radiation or drugs like Amiodarone or nitrofurantoin are also known associations with interstitial lung diseases, and of the systemic diseases, I think mostly of autoimmune diseases, so for example, scleroderma or lupus or the ANCA-associated vasculitides.
[Dr. Wiener] Well, let's assume for this case that he has no occupational or medication exposures, and he has no signs or symptoms of an autoimmune disease. Where do you go next? [Dr. Handy] Risk factors also help, for example, interstitial pulmonary fibrosis or IPF is rare among patients who are less than 50 years old. So it would seem that that's less likely here given the patient's age. A history of smoking is nearly always present in some forms of ILD.
For example, this would include respiratory bronchiolitis and desquamative interstitial pneumonia or DIP, sometimes referred by pathologists jointly as smoking-related ILD, where smoking is really thought to be causative. And a history of smoking is also noted in approximately three quarters of IPF patients. [Dr. Wiener] Does the CT help narrow things down a little bit? [Dr. Handy] In some cases it can. So for example, a lower lobe subpleural predominance is characteristic of IPF.
Some of the other potentially more reversible disorders have inflammatory nodules and ground-glass infiltrates, as in this case, and these changes are non-specific though. [Dr. Wiener] Again, these disorders are very confusing. [Dr. Handy] Yeah, and owing to a variety of clinical presentations as well as overlapping imaging and histopathologic findings, ILDs can be difficult to diagnose.
A generally accepted central tenant of ILD diagnosis is that the combined weight of clinical data, laboratory studies, pulmonary function testing, imaging findings, and histopathology if you're able to obtain it, are jointly required to make a confident diagnosis. But there isn't one single piece of data that confirms the diagnosis alone. [Dr. Wiener] So what do you think of this patient?
[Dr. Handy] Well, I don't think he has IPF given his age and CT, but given his extensive smoking, I'm thinking he likely has either respiratory bronchiolitis ILD, or the desquamative interstitial pneumonitis or perhaps a pulmonary Langerhans cell histiocytosis, which used to be known as eosinophilic granuloma. All of these disorders are directly tied to smoking. [Dr. Wiener] Okay, that's great.
Let's get to the question now, so the question asks, which of the following treatments would be most likely effective for his interstitial lung disease? And the options are, A. azathioprine; B. nintedanib; C. prednisone; D. sirolimus; or E. smoking cessation. [Dr. Handy] So based on our discussion, the answer in this case is E. Smoking cessation is often times the only treatment that's required to reverse the inflammatory process and the smoking-related interstitial lung diseases.
And patients can often start to improve within weeks of stopping smoking. [Dr. Wiener] What about the other therapies listed in the question? Do they have utility? [Dr. Handy] Well, at this point I would say that before resorting to the other therapies I'd give this patient a trial of smoking cessation, and if he doesn't improve in the next few weeks to months, I'd refer the patient to a specialist who's familiar with ILDs.
They're very difficult to treat and that being said, azathioprine is sometimes used for autoimmune diseases with associated ILD. Nintedanib is an anti-fibrotic tyrosine kinase inhibitor that has been shown in randomized clinical trials to reduce the rate of decline of FEC, and it can slow down the progression of idiopathic pulmonary fibrosis. And while it's currently being studied in a number of different ILDs, it is not yet shown to be effective in other disorders.
Prednisone is still used in some cases of ILD but certainly would not be first line treatment for this patient, and sirolimus has been used to treat LAM, but this disease is exceedingly uncommon in males and his chest CT is not consistent with that diagnosis. [Dr. Wiener] You mean, LAM being lymphangioleiomyomatosis? [Dr. Handy] Exactly. [Dr. Wiener] Yeah, that's a tough one to say. [both chuckle]
[Dr. Wiener] Okay, so the teaching point in this case is that the combination of reduced total lung capacity, and reduced DLCO is consistent with interstitial lung diseases. In this case, the history and the CT scan was suggestive of a smoking-related interstitial lung disease. And the mainstay of treatment in these cases is at least a trial of smoking cessation. [Dr. Handy] And to learn more about this, you can check out the Harrison's chapter on interstitial lung disease. [outro music]
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