acute interstitial pneumonia ( aip ) is an idiopathic lung disease characterized by rapidly progressive respiratory failure occurring in patients without pre - existing systemic or lung diseases with diffuse alveolar damage histologically ( 1 , 2 ) . since the term " acute interstitial pneumonia " was first introduced in 1986 ( 3 , 4 ) , some reported case reviews of aip ( 4 - 8 ) , with only 2 pediatric case reports ( 3 , 8) .
this is a case report of a 3-yr - old girl diagnosed as having aip from autopsy , whose two other siblings showed the similar radiological findings .
this is the first case report of aip in three children from the same family ; one of them was histologically confirmed , another was clinically and radiologically quite similar , and the other was radiologically suspected as having aip .
a 3-yr - old previously healthy girl presented with progressive dyspnea and chest discomfort . over the preceding 1 week , she had been admitted to a local general hospital for a sudden onset of dyspnea followed by 3 weeks of upper respiratory symptoms , mild rhinorrhea and dry cough without fever .
her 2-yr - old brother showed the same clinical symptoms presented at the same time ; however , she did not have any other known familial history of certain disease .
there was no evidence of systemic infection , immune suppression , exposure to toxic agents , pre - existing lung disease , or collagen - vascular disease . on physical examination
she showed tachypnea ( respiratory rate 48/min ) and chest wall retraction , and was requiring 5 l oxygen with face mask .
there were bilateral ground - glass opacification on simple chest radiograph and also bilateral ground - glass attenuation with diffuse alveolar consolidation on chest high - resolution computed tomography ( hrct ) ( fig .
arterial blood gas analysis gave ph 7.40 , pao2 88 mmhg , paco2 46 mmhg , sao2 96% ( 5
l / min of oxygen with face mask ) , and the white blood cell count was 9,330/l with 78% neutrophils .
c - reactive protein was negative , and other chemistry results were all within normal limits .
viral investigations including respiratory syncytial virus , adenovirus , influenza , parainfluenza , cytomegalovirus , ebstein - barr virus , herpes simplex virus , and evaluation for mycoplasma pneumoniae showed negative results .
rheumatoid factor and anti - nuclear antibody were both negative . under a presumptive diagnosis of interstitial lung disease , intravenous antibiotics and dexamethasone were administered . despite these
she presented with severe dyspnea and chest discomfort with pneumomediastinum and subcutaneous emphysema on chest radiograph .
pneumomediastinum was aggravated and resulted in pulmonary hemorrhage . because of ongoing hypoxemia and decreased mentality , endotracheal intubation was performed at 13th hospital day .
the patient died on the 14th day of admission after four times of cardiac arrest .
the histopathologic findings on autopsy of the lungs revealed diffusely thickened alveolar septal interstitium by uniform , organizing loose fibrosis and foci of hyaline membranes as well as prominent interstitial and alveolar edema with focal hyperplasia of type ii pneumocytes , which were indicative of organizing diffuse alveolar damage ( dad ) and episodes of acute lung injuries ( fig .
her 2-yr - old brother showed a same clinical course with diffuse bilateral ground - glass opacities on his hrct and also died after 4 weeks of intensive care due to respiratory failure aggravated by pneumothorax and subcutaneous emphysema .
it was unable to undergo any follow - up hrct , lung biopsy , or bronchoalveolar lavage because of his critical condition .
their 8-yr - old sister had no symptoms but underwent hrct for screening , which showed a mild degree of bilateral ground - glass opacities .
her pulmonary function test ( pft ) revealed patterns of restrictive lung disease . however , her follow - up hrct and pft showed improvement after five weeks of oral steroid administration .
in 1944 , hamman and rich initially described four previously healthy patients with fatal fulminant lung disease that , on autopsy , was characterized as extensive pulmonary fibrosis ( 8) . in 1986 , katzenstein and coworkers introduced the term " aip " to describe eight patients characterized by idiopathic interstitial lung disease causing a rapid onset of respiratory failure , which was distinguished from other chronic forms of interstitial pneumonia ( 3 ) .
since then , some reports have reviewed the cases of aip ( 4 - 8 ) , but among them , there were only 2 pediatric cases reports ( 4 , 8) showing a much lower incidence then in adult .
clinical manifestation of aip usually begins with prodromal ' flu - like ' upper respiratory infection symptoms , followed by rapid progression of dyspnea and respiratory failure that requires mechanical ventilation . in our case ,
the patient presented the same clinical course as in the previously reviewed cases ; beginning with mild cough and rhinorrhea , which was aggravated into respiratory failure requiring mechanical ventilation .
most of the cases reported as aip had extensive bilateral air - space opacification with sparing of costophrenic angles on their chest radiograph . as aip moves from exudative to organizing stage
, the radiograph shows less consolidation and presents a ground - glass appearance with irregular linear opacities ( 7 ) .
the most common ct findings in aip patients are diffuse ground - glass attenuation with a mosaic pattern and consolidation ( often in the dependent regions of the lungs ) ( 2 ) . in the early exudative phase ,
the lung shows areas of ground - glass attenuation that are most often bilateral and patchy , with areas of focal sparing of lung lobules giving a geographic appearance .
the later , organizing stage of aip is associated with distortion of bronchovascular bundles and traction bronchiectasis and cysts . in our case
, there was bilateral diffuse consolidation of lungs with peripheral sparing zones on chest radiograph , and chest hrct showed diffuse ground - glass opacities and consolidations with sparing zones in the peripheral portion of each lobe , suggesting the early exudative phase of aip .
this study was performed at the beginning of the patient 's respiratory difficulty , but follow - up hrct was not performed due to the patients critical condition .
even though we could not undergo another follow - up hrct , her chest radiograph showed an increase of bilateral haziness and findings of spontaneous pneumomediastinum and subcutaneous emphysema with bronchiectatic changes , suggesting a progression into the late organizing phase .
her 2-yr - old brother also showed same findings on chest ct , which was aggravated into bronchiectatic changes and pneumomediastinum on his chest radiograph .
their 8-yr - old sister who did not have any symptoms only showed a mild degree of bilateral ground - glass opacities without progression to bronchiectactic changes of lung parenchyma .
the histologic findings of aip include the features of acute and/or organizing phases of dad .
the exudative phase shows edema , hyaline membranes , and interstitial acute inflammation ( 7 ) . in the organizing phase , organizing fibrin , loose organizing fibrosis within alveolar lumens with incorporation within alveolar septa , and type ii pneumocyte hyperplasia are seen ( 2 ) . in this case , the patient underwent autopsy and histologic finings showed hyaline membrane with interstitial edema and proliferation of interstitial fibroblasts suggesting the presence of both acute exudative and late organizing phases .
treatment of aip is usually supportive and initially consists of oxygen supplement and noninvasive mechanical ventilation , but mechanical ventilation with positive - end - expiratory pressure is required in most patients .
patients are often treated with corticosteroids , which may improve the outcome as in patients with adult respiratory distress syndrome ( ards ) ( 1 ) .
treatment with newer agents such as surfactant , anti - cytokine antibodies , and inhaled nitric oxide traditionally used for ards , might be beneficial but are largely untested ( 3 ) .
however , we did not use any newer agents other than corticosteroids in this case . even though corticosteroid was not effective in two patients who died of aip , it was effective in their asymptomatic older sister who had an incidental finding of ground - glass opacities on chest ct .
her chest ct and pft findings were improved after administration of oral steroid agent . despite occurring in previously healthy persons ,
aip is associated with a poor prognosis ( 5 ) . according to a review of patient characteristics in the published series of aip by bouros et al . in 2000 , the mean 6-month mortality of patients with aip was 78% ( range , 60 - 100% ) ( 1 ) .
olson et al . reported a 41% survival rate from 29 patients ( 1 ) , two other small published series , total 2 of 13 patients survived ( 3 , 9 ) .
the prevalence of aip in childhood is rare , and only two cases of aip have been previously reported ; one of them survived after intravenous antibiotics and corticosteroid treatment ( 8) , and the other died on 40th day of admission ( 3 ) . in this case , the patient showed the same clinical course and radiologic , histologic findings as the previously reported aip cases in adults .
notably , two other siblings , her 2-yr - old brother and 8-yr - old sister , also showed the similar radiologic findings indicative of aip , even though they had some different degrees of symptoms and destruction of lung parenchyma . considering the coincidence in three children
however , we did not perform any genetic studies such as surfactant protein b and c. on the other hand , we could not exclude the possibility of an infectious origin , although the studies for infection were all negative . in summary , this rare case of aip in children gave us a chance to review the clinical course , radiologic and pathologic findings of aip in children , which showed no significant difference from those of adult cases in the literature ( 1 , 2 , 7 , 10 ) .
furthermore , we first experienced three different phases of aip in one family : one clinically , radiologically , and histoloically confirmed aip ; another clinically and radiologically highly suspected as having aip ; and the other only radioloically suspected as having aip .
 acute interstitial pneumonia ( aip ) is a rapidly progressive condition of unknown cause that occurs in a previously healthy individual and produces the histologic findings of diffuse alveolar damage . 
 since the term aip was first introduced in 1986 , there have been very few case reports of aip in children . here 
 we present a case of aip in a 3-yr - old girl whose other two siblings showed similar radiologic findings . the patient was confirmed to have aip from autopsy showing histological findings of diffuse alveolar damage and proliferation of fibroblasts . 
 her 3-yr - old brother was also clinically and radiologically highly suspected as having aip , and the other asymptomatic 8-yr - old sister was radiologically suspected as having aip . 
INTRODUCTION
CASE REPORT
DISCUSSION