Continuing Education Activity

Acute interstitial pneumonia is a form of idiopathic interstitial pneumonia with an acute onset and a rapidly progressive course that frequently leads to diffuse lung injury. This activity outlines the background, etiology, epidemiology, pathophysiology, presentation, and management options. We also highlight the role of the healthcare team in improving care for this condition.

Objectives:

• Outline the etiology of acute interstitial pneumonia.
• Describe the evaluation of acute interstitial pneumonia.
• Outline the management of acute interstitial pneumonia.
• Summarize the importance of improving communication and care coordination among the interprofessional team to improve outcomes for patients affected by acute interstitial pneumonia.

Introduction

Acute interstitial pneumonia (AIP - also known as Hamman-Rich syndrome) is an acute, rapidly progressive idiopathic pulmonary disease that often leads to fulminant respiratory failure and acute respiratory distress syndrome (ARDS).[1] It can be distinguished clinically from other types of interstitial pneumonia by the rapid onset of respiratory failure in a patient without preexisting lung disease.[2] Louis Hamman and Arnold Rich first described it in 1935 as a fulminating diffuse interstitial fibrosis of the lungs.[3] In 1986, Katzenstein introduced the term AIP differentiating it from the group of chronic interstitial pneumonia.[4][5] The American Thoracic Society (ATS) and European Respiratory Society (ERS) classify AIP under major idiopathic interstitial pneumonia, compared to other rare or unclassified idiopathic interstitial pneumonia.[1]

Etiology

Acute interstitial pneumonia (AIP) has no known etiology. 

Epidemiology

The mean age of patients with AIP is around 55. There is no sex predilection.[4][5][6][7][8][9]

Pathophysiology

Acute interstitial pneumonia (AIP) is thought to be triggered by an unknown insult to the alveolar epithelium leading to activation of the inflammatory cascade, followed by fibroblastic activity in the late stage.[6]

Histopathology

Acute interstitial pneumonia (AIP) has the histopathological pattern of diffuse alveolar damage (DAD) that is indistinguishable from the histologic pattern found in ARDS.[1][4][7] The histologic discerption depends on the timing of the biopsy. The early phase (within a week of the initial tissue injury) is exudative, characterized by edema in the interstitium and alveolus. After that, a late phase, which is also called the organizing phase, shows fibroblastic proliferation and type 2 cell hyperplasia.[2][4][7]

History and Physical

Symptoms usually start as viral-like prodrome followed with shortness of breath with cough, and fever, progress rapidly to acute respiratory distress. The physical exam is nonspecific with hypoxia, tachypnea, and bilateral diffuse crackles. Many of those patients are severely hypoxemic and require mechanical ventilation.[5][6][7][9] 

A detailed history with a comprehensive medical examination is essential to investigate for other causes of acute DAD, as noted below, under differential diagnosis.

Evaluation

Patients with Acute Interstitial Pneumonia are at risk of rapid respiratory decompensation. Vital signs should be monitored closely. Arterial blood gases can identify the severity of hypoxemia and the need for mechanical ventilation.  

Chest X-ray usually shows a pattern that is similar to ARDS, which is a bilateral air-space diffuse opacities. Therefore, ruling out cardiac causes of pulmonary edema is essential. Echocardiography is needed to rule out underlying cardiomyopathy or valve dysfunction.  High-Resolution Computed Tomography (HRCT) is usually abnormal in the first 12 hours. It shows ground-glass opacities and air space consolidation that can be diffuse or patchy. HRCT findings correlate with the different phases of DAD.[8][10][11][12] CT findings can also show traction bronchiectasis, indicating progression from the exudative phase to the proliferative fibrotic phase.[11]  

Laboratory workup should include screening for autoimmune and connective tissue diseases that might be associated with lung disease, starting from rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) to dermatomyositis and Sjogren syndrome.[13]

Microbiologic workup should include blood and sputum culture. Influenza screening is important, as well as serology for atypical organisms and fungus. Legionella is an atypical organism that can be detected on urine antigen test. Bronchoscopy with bronchoalveolar lavage (BAL) is needed to exclude diffuse alveolar hemorrhage (DAH), eosinophilia, or malignant infiltrates. In acute interstitial pneumonia, BAL results are usually non-specific with neutrophilia and scattered atypical type II pneumocytes.[14] Bronchoscopy also helps in obtaining respiratory samples for culture in the absence of sputum production. The sample should be sent for cell count and cytology, cultures, and Pneumocystis jirovecii immunofluorescence.  

If the previous workup fails to achieve an alternative diagnosis, lung biopsy might be indicated. Lung biopsy might also reveal different etiologies like caseating granulomas (tuberculosis), non-caseating granulomas (sarcoidosis), necrosis (vasculitis), abscesses, or viral inclusion.   

Acute interstitial pneumonia is an idiopathic disease. After excluding other causes of ARDS, pathologic confirmation of idiopathic DAD is necessary to establish the diagnosis.

Treatment / Management

There is no proven treatment in AIP.[1] Management is largely based on supportive care. Adequate oxygenation often cannot be achieved without mechanical ventilation.[9][15] As in ARDS, arterial blood gases can identify the severity of respiratory distress based on the Berlin Criteria (PaO2/FiO2).[16][17] Ventilator management mainly focuses on low tidal volume ventilation and other advanced ventilator modalities such as those used in ARDS.[16][17] 

Broad-spectrum antibiotics are recommended initially until infectious etiology is excluded.

Despite that steroid therapy is usually started empirically, it has no clear benefit in AIP. In a case series of 29 patients with AIP, 12 patients survived. Survival was 45% compared to 33% in patients who did vs. did not receive steroids, respectively.[7] Meanwhile, the mortality was 100% in a different case series of 9 patients who all received IV methylprednisolone 2 mg/kg 4 times a day.[15] 

Extracorporeal membrane oxygenation (ECMO) and lung transplantation should be considered for appropriate candidates after failing conventional therapy.[9][15][18]

Differential Diagnosis

Differential diagnosis of acute interstitial pneumonia includes:

• Other causes of interstitial pneumonia such as cryptogenic organizing pneumonia, acute eosinophilic pneumonia, and hypersensitivity pneumonitis
• Acute exacerbation of underlying interstitial lung disease or pulmonary exacerbation of a connective tissue disease
• Acute heart failure
• Infections
• Diffuse alveolar hemorrhage
• Drug-induced lung injury
• Radiation-induced lung injury

Prognosis

The mortality rate is greater than 50%, either in the initial presentation or within six months after onset. [1][4][5][7][9][15] Also, in survivors, recurrence, and development of chronic interstitial lung disease were reported.[9]

Deterrence and Patient Education

• Acute interstitial pneumonia is a disease with unclear causes, so it is hard to prevent or predict its onset
• Initial Symptoms are non-specific to the disease as any other respiratory disease.
• Patients should seek medical advice earlier before respiratory deterioration. 
• There is no specific test for acute interstitial pneumonia, and the only way to confirm it is a lung biopsy. 
• There is no specific medication to treat acute interstitial pneumonia. Management is generally supportive. 

Pearls and Other Issues

• AIP usually has a similar presentation to ARDS.
• AIP is only diagnosed after excluding other etiologies of diffuse alveolar hemorrhage.
• There is no specific treatment for AIP. Management is mostly supportive.
• Empiric broad-spectrum antibiotics should be started empirically until infection is excluded.
• A lung-protective strategy should be implemented.
• Treatment with steroids has no clear benefit in AIP.
• Mortality is high, and lung transplant should be considered for appropriate candidates. 

Enhancing Healthcare Team Outcomes

Acute interstitial pneumonia is an uncommon disease that presents acutely and progresses rapidly with a high rate of mortality. Diagnosis is complex and requires an interprofessional team, including pulmonology, radiology, and pathology. Proper communication and coordination between members of the healthcare team can fasten the diagnosis process, and therefore initiate the management earlier. The primary team also should be aware of the possible complication that may arise during the acute illness. Generally, the medical community still needs a better understanding of the initial triggers and progression of the disease to improve the outcome.