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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
Acute interstitial pneumonia : AIP
 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
Historical perspective and case definition
 In 1935, Hamman and Rich
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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
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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
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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
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The characteristic lesion of AIP is organizing diffuse alveolar damage
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the lesions appear homogeneous, derived from a single common insult
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Interstitial thickening is common and may obscure normal anatomic
landmarks.
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Air spaces are visible but reduced to slit like openings or completely
atelectatic
Pathology
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The interstitial thickening represents a combination of edema,
inflammatory cell infiltrate, fibroblast proliferation, and immature collagen.
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The interstitial inflammatory cells are predominantly mononuclear.
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alveolar type II cell hyperplasia, hyaline membrane remnants
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honeycomb fibrosis in advanced cases
Pathogenesis
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Much of the current understanding of AIP is derived from studies of acute lung
injury in animal models and human studies of ARDS.
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The initial injury is associated with alveolar epithelial cell damage and death
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the release of inflammatory mediators, such as tumor necrosis factor a (TNF-),
interleukin 1, and monocyte chemoattractant protein-1.
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Cytokine release, in turn, serves to amplify the inflammatory response.
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The result is neutrophil margination within pulmonary capillaries and
subsequent migration into the alveolar septa and alveolar spaces.
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Loss of the alveolar epithelial barrier allows alveolar type II cell hyperplasia,
hyaline membrane remnants
Pathogenesis
Epidemiology
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The disease occurs equally in men and women.
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Most affected patients are adults; the mean age at symptom onset was
54 years among the 138 reported cases.
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Approximately half of all patients seek medical attention within 1 week
of symptom onset.
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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
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Bronchoalveolar lavage (BAL) is an important early test and ideally is
performed within 24 hours of admission.
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BAL fluid should be sent for culture of typical respiratory pathogens,
including viruses, and for analysis of cellularity.
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BAL cellularity can be helpful in excluding the diagnosis of AIP and, in
some cases, may prove diagnostic.
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There is a neutrophil predominance, but neutrophilia also may be
seen with infectious processes and ARDS.
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the BAL findings of AIP are not specific.
Differential diagnosis
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In the absence of a definitive diagnosis by BAL, surgical lung biopsy
should be entertained.
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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.
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Methylprednisolone has been shown to improve survival in
fibroproliferative ARDS.
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the combination of cyclosporin, azathioprine, and prednisolone
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interferon--1
Survival
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
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several histopathologic features, including degree of interstitial fibrosis,
and found no correlation with survival.
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serum concentrations of cytokeratin 19 fragment (CK19) are increased
in AIP subjects compared with normal and idiopathic pulmonary fibrosis
subjects.
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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
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Olson et al
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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
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five survivors were asymptomatic but all had stable, residual disease by
chest radiograph
all four tested showed mild restrictive lung function.
Idiopathic ARDS & AIP
Diffuse alveolar damage
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Some patients with AIP can become
too ill to tolerate an open-lung
biopsy and go undiagnosed
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the incidence of AIP is probably
underestimated, as the diagnosis is
applied only to those in whom an
open-lung biopsy has been
performed.
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The term idiopathic ARDS has been
applied to patients who meet the
diagnostic criteria for AIP yet lack a
tissue diagnosis.
AIP
Idiopathic ARDS