AIP acute interstitial pneumonia

  • acute interstitial pneumonia (AIP)
    • acute/subacute, rapid few months
    • ARDS mimic without a clear cause
    • really sick
    • treat with steroids

This patient is presenting with an ARDS-like picture without an obvious inciting factor for ARDS or acute lung injury (eg, infection, trauma, pancreatitis, vaping, drug toxicity, inhalation injury, collagen vascular diseases), a neutrophilic predominant BAL, with negative microbiological findings, and no evidence of other causes of alveolar opacities such as hydrostatic pulmonary edema, diffuse alveolar hemorrhage, acute eosinophilic pneumonia, acute hypersensitivity pneumonitis, or acute exacerbation of pulmonary fibrosis. This presentation is consistent with a diagnosis of acute interstitial pneumonia (AIP), also referred to as the Hamman-Rich syndrome (choice A is correct). AIP is a rare and often fatal disease that can mimic ARDS. The cause is unknown, and AIP is sometimes defined as the development of ARDS in the absence of known triggers. The pathogenesis of AIP is neutrophilic damage to the epithelium of the alveolar membranes, followed by accumulation of exudate in the airspaces. Histologic examination reveals diffuse alveolar damage with intraalveolar hyaline membrane formation, interstitial and intraalveolar edema, acute inflammation, and epithelial cell necrosis with a nonspecific distribution and temporal uniformity (which supports a single acute injury as a cause). This process can progress to an organizing phase, characterized by alveolar septal thickening, type 2 pneumocyte hyperplasia, and fibroblast proliferation along the interstitium and alveolar spaces, and later it can progress to a fibrotic phase with alveolar septal thickening from organizing fibrosis.

AIP occurs in equal frequency in men and women, typically in previously healthy individuals in the 50 to 55-year age range. It develops acutely to subacutely over a few days to a few weeks. The mean duration of symptoms is 7 to 15 days. Dry cough, shortness of breath, malaise, and fever (in 75% of patients) are typical clinical findings. Crackles are heard on physical examination, and hypoxemia is characteristic. Clubbing is rare. Leukocytosis may be present. AIP often progresses to hypoxemic respiratory failure, and ICU admission with mechanical ventilation is usually required. Early mortality rates are high. Radiographic features of AIP include diffuse alveolar opacities and airspace consolidation similar to the appearance of ARDS and other alveolar filling processes (Figure 1). CT scans reveal bilateral airspace consolidation with areas of ground-glass opacities with little honeycombing.

The clinical diagnosis of AIP is made in the appropriate setting in a patient who has a clinical presentation compatible with ARDS but without a clear cause or trigger. Results of bronchoscopy with BAL in AIP are characterized by neutrophilic predominance. In a small number of cases, transbronchial biopsy may yield the diag­nosis, but definitive diagnosis in most cases of AIP requires a surgical lung biopsy revealing diffuse alveolar damage, although biopsies are not often performed. Treatment includes supportive ICU management. In small case series, high-dose corticosteroids with or without cyclophosphamide have been administered, but the mortality rate remains higher than 50% to 70%. Recurrences are possible, and some cases of AIP may resolve without sequelae, but in some series, more than 50% of survivors may be left with residual fibrosis.

If AIP is suspected, both the history and often bronchoscopy with BAL are important to exclude alternate diagnoses. Acute eosinophilic pneumonia is associated with exposure to dust, new onset or resumption of tobacco use, vaping, and smoke exposure and manifests with 5 to 7 days of fever, cough, and shortness of breath and progresses to respiratory failure. Early on, peripheral eosinophilia is absent, but BAL eosinophilia >20% is supportive of the diagnosis (choice D is incorrect). Diffuse alveolar hemorrhage is associated with coagulopathy, collagen vascular diseases, cocaine use, and some medications, and after stem cell transplant, it is associated with a drop in hemoglobin concentration, sometimes with hemoptysis, and is diagnosed with a progressively bloodier BAL on serial BALs and hemosiderin-laden macrophages in the BAL (choice B is incorrect). Hydrostatic pulmonary edema would likely be associated with an elevation in brain-type natriuretic peptide levels and abnormal cardiac findings (choice C is incorrect). Community-acquired pneumonia, although not offered as a choice in this question, would usually be associated with purulent material in sputum and on BAL and positive cultures and would likely not be this confluent radiographically unless complicated by ARDS; it also would usually have an elevated procalcitonin level. In lung toxicity from vaping, lipid-laden macrophages are sometimes seen on BAL.1234

Footnotes

  1. SEEK Questionnaires ↩

  2. Batra K, Butt Y, Gokaslan T, et al. Pathology and radiology correlation of idiopathic interstitial pneumonias. Hum Pathol. 2018;72:1-17. PubMed ↩

  3. Mukhopadhyay S, Parambil JG. Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS). Semin Respir Crit Care Med. 2012;33(5):476-485. PubMed ↩

  4. Travis WD, Costabel U, Hansell DM, et al; ATS/ERS Committee on Idiopathic Interstitial Pneumonias. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188(6):733-748. PubMed ↩