A 67-year-old man comes to the office due to slowly worsening fatigue and shortness of breath. The symptoms began after a chest cold 8 months ago. Medical history is significant for type 2 diabetes mellitus, for which the patient takes metformin. He has a 25-pack-year smoking history and quit 2 years ago. The patient is a retired attorney. He started taking trumpet lessons 3 months ago. Temperature is 36.6 C (97.9 F), blood pressure is 122/80 mm Hg, pulse is 70/min, and respirations are 16/min. Oxygen saturation is 96% on room air. Heart sounds are normal. Pulmonary examination demonstrates fine inspiratory crackles. Muscle strength is 5/5 throughout. The joints appear normal with full range of motion. Skin examination is normal. A high-resolution CT scan of the chest reveals lower lobe subpleural honeycombing and reticular markings greatest at the periphery. Pulmonary function tests demonstrate moderate restriction and reduced diffusion lung capacity for carbon monoxide. Hemoglobin A1c is 8.2%. All other laboratory test results are within normal limits. What is the most appropriate therapy for this patient?

Question

A 67-year-old man comes to the office due to slowly worsening fatigue and shortness of breath.  The symptoms began after a chest cold 8 months ago.  Medical history is significant for type 2 diabetes mellitus, for which the patient takes metformin.  He has a 25-pack-year smoking history and quit 2 years ago.  The patient is a retired attorney.  He started taking trumpet lessons 3 months ago.  Temperature is 36.6 C (97.9 F), blood pressure is 122/80 mm Hg, pulse is 70/min, and respirations are 16/min.  Oxygen saturation is 96% on room air.  Heart sounds are normal.  Pulmonary examination demonstrates fine inspiratory crackles.  Muscle strength is 5/5 throughout.  The joints appear normal with full range of motion.  Skin examination is normal.  A high-resolution CT scan of the chest reveals lower lobe subpleural honeycombing and reticular markings greatest at the periphery.  Pulmonary function tests demonstrate moderate restriction and reduced diffusion lung capacity for carbon monoxide.  Hemoglobin A1c is 8.2%.  All other laboratory test results are within normal limits.  What is the most appropriate therapy for this patient?

Quizplus · Accepted Answer

11ec25c8_d824_7f37_bc81_4b8d9b32f043_MD0003_00 This patient with dyspnea and inspiratory crackles has pulmonary restriction and a high-resolution CT (HRCT) of the chest showing a pattern of subpleural honeycombing and reticular opacities (ie, usual interstitial pneumonia [UIP]). There is no evidence for underlying connective tissue disease (ie, normal skin and joint examinations) or history of relevant exposure (eg, asbestos, pneumotoxic drugs). This presentation is most consistent with idiopathic pulmonary fibrosis (IPF), diagnosed when UIP is present on HRCT and secondary causes of UIP (eg, autoimmune disease, exposures) have been excluded. IPF can be a devastating diagnosis; average survival is 2-3 years. Central to IPF pathogenesis is alveolar epithelial injury that is inappropriately repaired by fibrosis (scarring). Antifibrotic therapy has revolutionized IPF treatment. These small-molecule inhibitors block profibrotic growth factor signaling (eg, transforming growth factor β), reducing fibroblast proliferation and collagen production. They are approved for IPF patients with diminished lung function, such as reduced forced vital capacity (FVC). Antifibrotic drugs slow the rate of FVC decline but cannot restore lost lung function. Candidates for treatment should be identified early and monitored closely for progression. (Choices B and D) Because low levels of lung inflammation are common in IPF, pharmacologic immunosuppression was once regarded as a promising treatment strategy. However, inflammatory responses are likely reactive to the primary epithelial injury and fibrosis. Clinical trials of immunosuppression (eg, prednisone [corticosteroid], azathioprine [noncorticosteroid]) demonstrated harm, including increased mortality. If lung fibrosis is suspected to be driven by a systemic autoimmune disease (eg, scleroderma-associated UIP), immunosuppression is considered on an individual basis. Forms of ILD that tend to be corticosteroid-responsive include cryptogenic organizing pneumonia (eg, groundglass/consolidative opacities on HRCT, alveolar granulation tissue on histopathology). (Choice C) Exposure to organic antigens can cause hypersensitivity pneumonitis (HP). Acute HP presents with short-lived episodes following exposure. Chronic HP can develop with continued exposure causing fibrotic evolution; it can be seen in wind instrument (eg, bagpipe, rather than trumpet) players due to mold overgrowth. However, the timeline of this patient's symptoms (8 months) does not correspond to exposure (started lessons 3 months ago), and the radiographic pattern (ie, lower lobe honeycombing, peripheral reticular markings) revealed by HRCT scanning is specific for UIP rather than HP. (Choice E) Although IPF survival is limited, antifibrotic therapy should be considered, especially in patients with good functional status who may also be eligible for lung transplantation. Hospice care may become appropriate when life expectancy is ≤6 months. Educational objective: Idiopathic pulmonary fibrosis is a disorder of epithelial injury that has been pathologically repaired by fibrotic responses. Antifibrotic drugs inhibit fibroblasts to slow the rate of lung function decline and are first-line therapy.

A 67-Year-Old Man Comes to the Office Due to Slowly