Acute interstitial pneumonia Jason S. Vourlekis, MD Section of Pulmonary Medicine, National Naval Medical Center, Bethesda, MD, USA Clin Chest Med 25 (2004) 739 – 747

Diffuse parenchymal lung disease

Idiopathic interstitial pneumonia

ATS/ERS in 2000

 its contemporary description nearly 20 years ago  knowledge of this peculiar disease has increased little.  very rapid to fulminant onset  high fatality ratio  more favorable long-term prognosis for survivors Acute interstitial pneumonia : AIP

Historical perspective and case definition  In 1935, Hamman and Rich original report of four cases rapidly progressive fibrotic lung disease with a common histologic pattern. Hamman-Rich syndrome : progressive pulmonary fibrosis of unknown etiology synonymously with idiopathic pulmonary fibrosis  In 1975 Liebow more rapid forms of pulmonary fibrosis,including Hamman-Rich syndrome subsumed under the classification of usual interstitial pneumonia.

Historical perspective and case definition In 1986, Katzenstein and Myers  acute respiratory failure case  organizing diffuse alveolar damage on pathologic examination of lung tissue  ‘acute interstitial pneumonitis’ Olson et al  reviewed three of Hamman and Rich’s original cases  the pathologic lesion as organizing diffuse alveolar damage  AIP and Hamman-Rich syndrome as the same entity  distinguish AIP from idiopathic pulmonary fibrosis

Historical perspective and case definition in 2000, ATS/ERS  AIP as distinct from idiopathic pulmonary fibrosis  rapid symptom onset, unknown causation  the presence of organizing diffuse alveolar damage on biopsy  same clinical features late phase of ARDS  AIP is a diagnosis of exclusion

Pathology  The characteristic lesion of AIP is organizing diffuse alveolar damage  the lesions appear homogeneous, derived from a single common insult  Interstitial thickening is common and may obscure normal anatomic landmarks.  Air spaces are visible but reduced to slit like openings or completely atelectatic

Pathology  The interstitial thickening represents a combination of edema, inflammatory cell infiltrate, fibroblast proliferation, and immature collagen.  The interstitial inflammatory cells are predominantly mononuclear.  alveolar type II cell hyperplasia, hyaline membrane remnants  honeycomb fibrosis in advanced cases

Pathogenesis  Much of the current understanding of AIP is derived from studies of acute lung injury in animal models and human studies of ARDS.  The initial injury is associated with alveolar epithelial cell damage and death  the release of inflammatory mediators, such as tumor necrosis factor a (TNF-  ), interleukin 1 , and monocyte chemoattractant protein-1.  Cytokine release, in turn, serves to amplify the inflammatory response.  The result is neutrophil margination within pulmonary capillaries and subsequent migration into the alveolar septa and alveolar spaces.  Loss of the alveolar epithelial barrier allows alveolar type II cell hyperplasia, hyaline membrane remnants

Pathogenesis

Epidemiology  The disease occurs equally in men and women.  Most affected patients are adults; the mean age at symptom onset was 54 years among the 138 reported cases.  Approximately half of all patients seek medical attention within 1 week of symptom onset.  In contrast, another 25% seem to have more indolent symptom progression, a subset of patients has a subacute presentation.

Clinical course  A flu-like prodrome ; headache, myalgia, sore throat, malaise, and cough. fever (some cases)  The development of dyspnea often follows within a few to several days.  Most have tachycardia, tachypnea, and signs of hypoxemia.  Crackles and wheezes have been reported on chest examination.  Most hypoxemic progressive respiratory failure, requiring mechanical ventilation

Differential diagnosis  Bronchoalveolar lavage (BAL) is an important early test and ideally is performed within 24 hours of admission.  BAL fluid should be sent for culture of typical respiratory pathogens, including viruses, and for analysis of cellularity.  BAL cellularity can be helpful in excluding the diagnosis of AIP and, in some cases, may prove diagnostic.  There is a neutrophil predominance, but neutrophilia also may be seen with infectious processes and ARDS.  the BAL findings of AIP are not specific.

Differential diagnosis  In the absence of a definitive diagnosis by BAL, surgical lung biopsy should be entertained.  In patients considered too critically ill for biopsy, it is reasonable to consider empiric therapy with corticosteroids alone.

Therapy  There are no established therapies for AIP.  Parenteral corticosteroids, often at high doses, are used frequently but their efficacy is unproven. Methylprednisolone has been shown to improve survival in fibroproliferative ARDS. the combination of cyclosporin, azathioprine, and prednisolone interferon-  -1 

Survival

 The acute case fatality ratio for AIP is approximately 70%.  In North American studies, the fatality ratio is 12.5% to 62% and is even higher in international studies.  The mortality from AIP is greater than ARDS.

Survival  several histopathologic features, including degree of interstitial fibrosis, and found no correlation with survival.  serum concentrations of cytokeratin 19 fragment (CK19) are increased in AIP subjects compared with normal and idiopathic pulmonary fibrosis subjects.  CK19 is a marker of lung epithelial cell injury. too small to make any meaningful correlation with survival.

Long-term prognosis  Although there is little longitudinal data on AIP, the available information suggests that survivors seem to follow one of four patterns: (1) complete recovery of lung function (2) stable but persistent abnormalities in lung function (3) progressive pulmonary fibrosis (4) recurrent AIP

Long-term prognosis  Olson et al At least six of twelve survivors were confirmed alive and well at 2 years. Pulmonary function tests show persistent but stable restrictive physiology in two patients.  Quefatieh et al five survivors were asymptomatic but all had stable, residual disease by chest radiograph all four tested showed mild restrictive lung function.

Idiopathic ARDS & AIP  Some patients with AIP can become too ill to tolerate an open-lung biopsy and go undiagnosed  the incidence of AIP is probably underestimated, as the diagnosis is applied only to those in whom an open-lung biopsy has been performed.  The term idiopathic ARDS has been applied to patients who meet the diagnostic criteria for AIP yet lack a tissue diagnosis. Idiopathic ARDS AIP Diffuse alveolar damage