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Nonspecific Interstitial Pneumonitis or Hypersensitivity Pneumonitis?

Case Editor - Victor Kim

Reviewed By Environmental & Occupational Health Assembly

Submitted by

Erica Hughes, MD

Senior Pulmonary Fellow

University of Texas Southwestern Medical Center

Dallas, Texas

Craig Glazer, MD, MSPH, FCCP

Assistant Professor of Medicine

University of Texas Southwestern Medical Center

Dallas, Texas


A 51-year-old man initially presented with dyspnea and dry cough. He denied any constitutional symptoms including fevers, chills, arthralgias, myalgias, night sweats and weight loss. His primary care physician initially treated him with antibiotics without response. The dyspnea on exertion and cough continued to progress over the next several months.

His past medical and surgical history was unremarkable. His family history was positive for sarcoidosis. He was taking no medication and was a nonsmoker. He had no allergies. His occupational history was significant for working in a hospital for many years, and he was not exposed to workplace agents associated with interstitial lung disease.

After several months of symptoms unresponsive to antibiotics, a chest radiograph was performed and revealed interstitial disease. He was subsequently referred to a pulmonologist who performed pulmonary function tests that showed restriction and a severely reduced diffusion capacity.

Physical Exam

Vital Signs

temperature                     36.7°C
respiration                        20
pulse                                120
blood pressure                 126/87
oxygen saturation            92%  (room air)

Although tachypneic, he was not using his accessory muscles. HEENT was unremarkable. Chest examinations indicated symmetric excursions and expansion, resonant to percussion bilaterally. There were bilateral inspiratory crackles halfway up the chest posteriorly. His heart rhythm was regular and he had no murmur or gallop. His abdomen was soft with normal bowel sounds and no organomegaly. His extremities were without cyanosis, clubbing or edema. His skin and joint exams were unremarkable.


Pulmonary function tests

FVC                 2.44 (51%)
FEV1               2.07 (54%)
FEV1/FVC        0.85
DLCO              26% predicted
TLC                 3.53 (45%)

A high-resolution computed tomography (HRCT) of the chest showed diffuse ground-glass opacities with bibasilar fibrotic changes. A bronchoscopy with bronchoalveolar lavage and transbronchial biopsy revealed 30% lymphocytes and nondiagnostic pathology. An open lung biopsy revealed fibrotic nonspecific interstitial pneumonia (NSIP). Prednisone was started with some initial symptomatic improvement. His symptoms, however, progressed again despite continued prednisone, and he was referred to our institution for a second opinion. At the time we evaluated him, his symptoms were present 1 year and had continued to progress despite the treatment with prednisone. His physical examination revealed diffuse inspiratory crackles and he required continuous supplemental oxygen because of resting hypoxemia.

His connective tissue serologies were negative, but on further questioning, he admitted buying two parakeets for his family 3 months before the onset of symptoms. Precipitins to parakeet droppings were negative. The birds were removed from his home, and his house, including the heating and air conditioning system, was professionally cleaned. The house had no carpet in the area where the birds were housed. Azathioprine was added to his prednisone, starting at 50 mg/day with plans to increase the dose over a 2 month period if needed. One month later, his symptoms were markedly improved and his supplemental oxygen was discontinued. His prednisone and azathioprine were weaned over the next year. He is now stable off all therapy.


Chest radiograph shows bilateral reticular markings and an elevated left hemidiaphragm

Question 1

Which of the following are NOT in the differential diagnosis for a pathologic diagnosis of NSIP?


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