Nonspecific Interstitial Pneumonitis Research Articles

Rapid Recurrence of Interstitial Fibrosis Following Lung Transplantation

INTRODUCTION: Common causes of dyspnea in the first year following lung transplantation include infection, acute rejection, bronchiolitis obliterans and bronchial strictures. Recurrence of primary lung disease is uncommon and rarely clinically significant. We report a case of recurrence of fibrosing nonspecific interstitial pneumonitis in a transplanted lung.

Das Anti-Jo-1-Syndrom – eine Sonderform der Myositis mit interstitieller Lungenerkrankung

Interstitial lung disease (ILD) may be associated with systemic inflammatory disorders and autoantibody production. The development of ILD has been described in detail in patients with polymyositis and dermatomyositis. Anti-synthetase antibodies, including anti-Jo-1 antibodies (antihistidyl-tRNA syntase), are found in up to 35 % of patients with myositis, 80 % of which constitute anti-Jo-1 antibodies. The anti-Jo-1 syndrome characteristically presents with myositis, shortness of breath, fever, polyarthritis/arthralgia, mechanic's hands, dermatomyositis-like skin lesions, signs of a connective tissue disease and/or Raynaud's phenomenon. ILD is an early diagnostic sign and shows focal infiltrates and an acinar pattern in CT scan. Non-specific interstitial pneumonitis with T-lymphocytic infiltrates in lung histology (VATS) or elevated IFN-gamma-inducible chemokines are further indicators for anti-Jo-1 syndrome. Corticosteroids eventually combined with an immunosuppressant drug are often required with reported beneficial effects, although not many therapeutic studies have been performed. Here we present a review of the current literature and a case report on anti-Jo-1 syndrome.

Nonspecific Interstitial Pneumonitis after Bortezomib and Thalidomide Treatment in a Multiple Myeloma Patient

Bortezomib, an inhibitor of 26S proteosome, is recently approved treatment option for multiple myeloma. Thalidomide, a drug with immunomodulating and antiangiogenic effects, has also shown promise as an effective treatment in multiple myeloma. Pulmonary complications are believed to be rare, especially interstitial lung disease. Here, we describe a patient with dyspnea and diffuse pulmonary infiltrates while receiving bortezomib and thalidomide in combination with dexamethasone for treatment-naïve multiple myeloma. Bronchoalveolar lavage demonstrated a significant decrease in the ratio of CD4 : CD8 T lymphocytes (CD4/8 ratio, 0.54). Extensive workup for other causes, including infections, was negative. A lung biopsy under video-assisted thorascopic surgery revealed a diagnosis of nonspecific interstitial pneumonitis. The symptoms and imaging study findings improved after initiating steroid treatment. Physicians should be aware of this potential complication in patients receiving the novel molecular-targeted antineoplastic agents, bortezomib and thalidomide, who present with dyspnea and new pulmonary infiltrates and fail to improve despite treatment with broad-spectrum antibiotics.

Pathologic study of diffuse pulmonary interstitial fibrosis caused by chronic hypersensitivity pneumonitis

To study the pathologic characteristics of chronic hypersensitivity pneumonitis, especially the pattern of pulmonary interstitial fibrosis; and to compare the histologic features with those of idiopathic interstitial pneumonitis. The HE-stained paraffin sections of 10 cases of chronic hypersensitivity pneumonitis encountered during the period from 2000 to 2008 were retrospectively analyzed. There were altogether 6 males and 4 females, with age of patients ranging from 23 to 59 years (mean=47.2 years). Clinically, the patients presented with chronic cough and shortness of breath for 4 months to 6 years. Histologically, 7 cases showed usual interstitial pneumonitis (UIP)-like fibrosis. Patchy fibrosis was observed under the pleura, adjacent to interlobular septa and around bronchioles. In all of the 7 cases, foci of fibroblastic proliferation, as well as bronchiolar metaplasia of peribronchiolar alveoli and mild bronchiolitis, were noted. Three cases presented with mild honeycomb changes of lung and 3 cases showed non-specific interstitial pneumonitis (NSIP)-like fibrosis, in which the alveolar septa were expanded by fibrous tissue and collagen, with relative preservation of alveolar architecture. Bronchiolitis and lymphocytic infiltrates in alveolar septa were seen. Schaumann bodies were identified in 1 case. In general, patients with chronic hypersensitivity pneumonitis were younger than patients with idiopathic UIP. Computed tomography often showed upper and middle lobar involvement and mosaic attenuation. Compared with idiopathic UIP, the UIP-like fibrosis of chronic hypersensitivity pneumonitis often occurred not only under the pleura and adjacent to interlobular septa, but also around bronchioles and was accompanied by bronchiolar metaplasia. Chronic hypersensitivity pneumonitis can mimic other types of lung conditions with interstitial fibrosis, especially UIP and NSIP. As a result, some cases of chronic hypersensitivity pneumonitis may be misdiagnosed as such.

Bronchiolitis obliterans organizing pneumonia: Pathogenesis, clinical features, imaging and therapy review

Bronchiolitis obliterans organizing pneumonia (BOOP) was first described in the early 1980s as a clinicopathologic syndrome characterized symptomatically by subacute or chronic respiratory illness and histopathologically by the presence of granulation tissue in the bronchiolar lumen, alveolar ducts and some alveoli, associated with a variable degree of interstitial and airspace infiltration by mononuclear cells and foamy macrophages. Persons of all ages can be affected. Dry cough and shortness of breath of 2 weeks to 2 months in duration usually characterizes BOOP. Symptoms persist despite antibiotic therapy. On imaging, air space consolidation can be indistinguishable from chronic eosinophilic pneumonia (CEP), interstitial pneumonitis (acute, nonspecific and usual interstitial pneumonitis, neoplasm, inflammation and infection). The definitive diagnosis is achieved by tissue biopsy. Patients with BOOP respond favorably to treatment with steroids.

Clinical, radiological and pathological features of ABCA3 mutations in children

Background:Mutations in the ABCA3 gene can result in fatal surfactant deficiency in term newborn infants and chronic interstitial lung disease in older children. Previous studies on ABCA3 mutations have focused...

Bronchiolitis interstitial pneumonitis: a pathologic study of 31 lung biopsies with features intermediate between bronchiolitis obliterans organizing pneumonia and usual interstitial pneumonitis, with clinical correlation

Bronchiolitis combined with interstitial pneumonitis generally has been equated with bronchiolitis obliterans organizing pneumonia (BOOP). We describe our experience with lung biopsies that had both bronchiolar and interstitial diseases. We studied 31 patients who had respiratory difficulty leading to open lung biopsy, which showed a combination of both prominent bronchiolitis and prominent interstitial pneumonitis. We compared these cases clinically and pathologically with 6 other pulmonary diseases, namely, bronchiolitis obliterans, BOOP, nonspecific interstitial pneumonitis, usual interstitial pneumonitis, airway-centered interstitial fibrosis, and idiopathic bronchiolocentric interstitial pneumonia, and with 10 cases of cystic fibrosis, an unrelated disease with both bronchiolar and interstitial pathology. The commonality of our cases was a combination of bronchiolitis and interstitial inflammation and fibrosis but little or no intra-alveolar organizing pneumonia. Bronchiolitis obliterans with organizing pneumonia involved less area than the interstitial pneumonitis in each case. All 19 patients for whom we had follow-up received corticosteroids for their pulmonary diseases. Seven patients had improvement in symptoms and pulmonary function test results and radiographic findings, 5 patients experienced subjective improvement with unchanged results of pulmonary function tests or chest x-ray, 1 patient's condition was unchanged, 6 patients' disease worsened, and 4 of these 6 died. The natural history of these cases, which we have designated bronchiolitis interstitial pneumonitis, seems more sanguine than usual interstitial pneumonitis and worse than BOOP at least in the short term. On the one hand, response to corticosteroids was not as frequent as generally accepted for BOOP. On the other hand, disease did not progress in most patients on corticosteroids.

The Role of Anti–Endothelial Cell Antibody–Mediated Microvascular Injury in the Evolution of Pulmonary Fibrosis in the Setting of Collagen Vascular Disease

We encountered 16 patients with connective tissue disease in whom pulmonary fibrosis developed. Routine light microscopic, ultrastructural, and direct immunofluorescent analyses were conducted, and circulating antibodies, including those of endothelial cell derivation, were assessed using indirect immuno-fluorescence and Western blot assays. Underlying diseases were dermatomyositis, scleroderma, mixed connective tissue disease, sclerodermatomyositis, Sjögren syndrome, rheumatoid arthritis, and anti-Ro-associated systemic lupus erythematosus. Antibodies to one or more Ro, RNP, Jo 1, OJ, and/or nucleolar antigens were seen in all cases and antiphospholipid antibodies in half. All biopsies revealed microvascular injury in concert with intraparenchymal fibrosis; in some cases, there were corroborative ultrastructural findings of microvascular injury. Patterns of fibroplasia represented nonspecific interstitial pneumonitis and usual interstitial pneumonitis. We noted IgG, IgA, and/or complement in the septal microvasculature. In 6 cases with available serum samples, indirect immunofluorescent endothelial cell antibody studies were positive and Western Blot studies showed reactivity of serum samples to numerous endothelial cell lysate-derived proteins. Pulmonary fibrosis, a recognized complication of systemic connective tissue disease, develops in connective tissue disease syndromes with pathogenetically established immune-based microvascular injury at other sites. A similar mechanism of antibody-mediated endothelial cell injury may be the basis of the tissue injury and fibrosing reparative response.

The etiology of nonspecific interstitial pneumonitis in acquired immunodeficiency syndrome

Summary Interstitial pneumonitis without evidence of Pneumocystis jiroveci infection has been described in the patients infected with immunodeficiency virus (HIV). Nonspecific interstitial pneumonitis (NSIP) is the most commonly observed pathologic diagnosis. The etiology of NSIP in HIV infected patients is unknown. We retrospectively studied 6 cases of NSIP that were diagnosed with transbronchial biopsies. The etiologic causes of NSIP were evaluated retrospectively by reviewing the inpatient and outpatient charts. The medical records from other institutions were also reviewed when available. We concluded that cocaine abuse, disseminated Mycobacterium avium complex infection, cytomegalovirus (CMV) pneumonitis, and immune reconstitution syndrome were the potential causes of NSIP in our patients with HIV infection.

Pneumocystis jiroveci pneumonia and other pulmonary infections in TB smear-negative HIV-positive patients with atypical chest X-ray in Ethiopia

Pneumocystis pneumonia (PCP) has been considered a rare disease in sub-Saharan Africa. However, a rising prevalence has been noted recently. The objective of this study was to determine the relative prevalence of PCP and other pulmonary opportunistic diseases in patients infected with HIV in Ethiopia. 131 consecutive patients with respiratory symptoms and atypical chest X-ray, who were sputum smear-negative for AFB and seroreactive for HIV, underwent clinical evaluation and investigation for Pneumocystis jiroveci and Mycobacterium tuberculosis from sputum and bronchoalveolar lavage (BAL), and fungal and bacterial pathogens from BAL alone. Bacterial infections, Pneumocystis pneumonia (PCP) and pulmonary tuberculosis (PTB) occurred in 44 (33.6%), 39 (29.7%) and 31 (23.7%) patients, respectively. Pulmonary Kaposi sarcoma and non-specific interstitial pneumonitis occurred in 4 patients each. In a multivariate regression model, predictors of PCP were typical chest X-ray and low CD4 count while purulent sputum predicted bacterial infection. The sensitivity of physicians and chest X-ray diagnosis was particularly low for PTB and bacterial infections. We conclude that chronic bacterial infection and Pneumocystis pneumonia are important differential diagnoses in HIV-infected, smear-negative PTB patients presenting with atypical chest X-ray. We therefore need to escalate the use of preventive and highly active antiretroviral (HAART) treatment in order to prevent a PCP epidemic.

Klinische, radiologische und histo-pathologische Kriterien zur differential-diagnostischen Abgrenzung der exogen-allergischen Alveolitis von der nicht-spezifischen interstitiellen Pneumonie

The non-specific interstitial pneumonitis (NSIP) is an important differential diagnosis of extrinsic allergic alveolitis (EAA). While the acute course of EAA in spite of similar bronchoalveolar lavage and radiological patterns can be clearly differentiated by serum antibodies and the temporal relationship between antigen contact and clinical symptoms, the chronic course of EAA is difficult to differentiate. Even by open lung biopsy a definite diagnosis can be established in all cases. Due to possible long-term consequences (antigen avoidance) however, an open lung biopsy should be performed in questionable cases.

Thoracic Lymph Node Enlargement in Usual Interstitial Pneumonitis and Nonspecific-interstitial Pneumonitis

To evaluate the prevalence of thoracic lymph node enlargement (LNE) in usual (UIP) and nonspecific (NSIP) interstitial pneumonitis, change in LNE over time, and if LNE is related to disease activity. High-resolution CT scans (HRCT) in 20 patients each with UIP and NSIP were retrospectively reviewed. Two HRCT scans were reviewed for each patient, at diagnosis and a mean of 1 +/- 0.7 years later. Two thoracic radiologists independently recorded the location and size of thoracic lymph nodes (LNs) > 10-mm in short-axis diameter, using the American Thoracic Society lymph node mapping scheme. HRCT disease severity was scored for ground glass opacity and fibrosis. The number and size of enlarged LN stations were compared with HRCT scores. LNE was found on 44 HRCT examinations (21 baseline prevalence 52.5%, 23 follow-up, prevalence 57.5%), most common in the low right paratracheal (38%) and subcarinal (36%) regions. There was no significant difference in LN size or number of enlarged LN stations between baseline and follow-up CT. LNE prevalence was not different on baseline CT (P = 0.34) follow-up CT (P = 0.11) between UIP and NSIP patients. The mean size of the largest enlarged LN was 1.36 cm (1 to 2.1 cm) at baseline and 1.43 cm (1 to 1.9 cm) on follow-up CT. Mean CT ground glass and fibrosis scores were 1.98 and 1.6 when LNE was present, and 1.34 and 1.03 when absent (P = 0.008 and 0.003, respectively). The number and maximum size of enlarged LNs did not correlate with CT ground glass or fibrosis scores. Five patients who developed LNE between baseline and follow-up CT examinations had a greater increase in CT fibrosis scores than patients whose LNE status did not change (P = 0.004); CT ground glass scores were not significantly different. There was a trend for UIP patients to progress from absence of LNE to presence of LNE (4/20 patients or 20%). Intrathoracic LNE is common in both UIP and NSIP, and becomes increasingly prevalent in UIP patients over time. LNE is more prevalent with more severe lung disease. An increase in LNE over time is associated with the progression of fibrosis, and should not raise concern for co-existing infection or malignancy, in the absence of other clinical findings that would suggest this.

Idiopathic Pulmonary Fibrosis Related to Endothelial Injury and Antiendothelial Cell Antibodies

Mechanisms underlying idiopathic pulmonary fibrosis are not well understood. This paper presents data supporting the hypothesis that microvascular endothelial cell injury and antiendothelial cell antibodies play roles in human idiopathic pulmonary fibrosis. Serologic and pathologic features of 40 patients diagnosed with idiopathic pulmonary fibrosis were evaluated. All patients had open lung biopsies indicating either usual or nonspecific interstitial pneumonitis. All biopsies had morphologic evidence of microvascular injury to the endothelium, and direct immunofluorescence testing revealed variable deposition of IgG, IgM, or IgA within septal microvasculature suggestive of humorally mediated microvascular injury. Ultrastructural studies revealed changes of endothelial cell injury and necrosis and evidence of repetitive episodes of microvascular injury characterized by basement membrane zone collagen deposition and lamellation. Serum samples demonstrated reactivity to multiple endothelial cell antigenic epitopes, and indirect immunofluorescent testing demonstrated a prominent pattern of fluorescence in pulmonary endothelial cell preparations. Serum samples were positive in 37/40 patients for antiphospholipid antibodies with one fourth having positive lupus anticoagulant tests accompanied by thrombotic episodes. In patients with idiopathic pulmonary fibrosis, Factor VIII levels and C-reactive protein levels were also elevated, supporting the presence of endothelial cell injury and inflammation. These data underscore a potential role for immune-based microvascular injury in the evolution of usual or nonspecific interstitial pneumonitis and indicate that those patients have evidence of microvascular injury and endothelial cell necrosis. The high prevalence of antiphospholipid antibodies in these patients may lead to an inherent thrombophilic tendency.

Differential epithelial expression of SHH and FOXF1 in usual and nonspecific interstitial pneumonia

Morphogenetic factors have been shown to play a role in embryogenesis and post-embryonic disease. Interstitial pulmonary fibrosis is a chronic and often progressive disorder that can lead to end-stage cystic lung. Its two major subtypes, usual interstitial pneumonitis (UIP) and nonspecific interstitial pneumonitis (NSIP) differ in their response to immunosuppressive regimens, with UIP having a significantly worse prognosis. The clinical and histologic overlap between these disorders is substantial, and there are no ancillary findings that can accurately distinguish them. We examined surgical and autopsy specimens of lung in 13 cases of patients with either UIP or the fibrotic variant of NSIP (NSIP-F) for their expression of Sonic hedgehog (Shh) and Foxf1 in situ. We identified a pattern of strong Shh expression with weak expression of Foxf1 in all cases of UIP and a complementary expression of Shh and Foxf1 in cases of NSIP-F. We conclude that morphogenetic genes may participate differentially in the pathogenesis of UIP and NSIP-F.

Pneumatosis Cystoides Intestinalis after .ALPHA.Glucosidase Inhibitor Treatment in a Patient with Interstitial Pneumonitis

A 56-year-old woman was admitted to our hospital for treatment of non-specific interstitial pneumonitis (NSIP). The patient started prednisone treatment, but one month later treatment with voglibose, an alpha-glucosidase inhibitor (alpha-GI), was started because of prednisone-induced diabetes mellitus. One week later, a massive volume of free air below the diaphragm was detected by a chest X-ray examination. An abdominal CT examination demonstrated pneumatosis coli and the patient was diagnosed with pneumatosis cystoides intestinalis (PCI). Voglibose was discontinued and parenteral nutrition and oxygen inhalation were initiated. Radiographic findings of PCI disappeared within 7 days. We encountered a rare case of PCI, that was associated with alpha-GI treatment.

Lung injury after airbag deployment: Airbag lung

A 37-year-old female presented to pulmonary clinic for evaluation of exertional dyspnea and cough. Nine months before presentation she was involved in motor vehicle accident as a driver. During the accident the driver side airbag deployed and ruptured. Hours after the accident, the patient experienced airway irritation and cough. As a result of the accident, she sustained back injury that required surgical intervention. Seven months before presentation, after recovery from surgery, she noticed shortness of breath with resumption of daily activities. Four months before presentation, she was evaluated in an emergency department for worsening dyspnea and cough and received treatment. She noticed only transient and minimal improvement in her symptoms. She was a lifelong non-smoker and had no known occupational exposures. Upon opur evaluation, a computed tomography (CT) of the chest was performed that revealed patchy bilateral ground-glass infiltrates and consolidations. These findings suggest interstitial and alveolar inflammation. Dry cough, dyspnea on exertion, restrictive physiology, and diffuse ground-glass infiltrates on CT scan is characteristic of interstitial lung disease (ILD). A lung biopsy was obtained by video-assisted thoracoscopy surgery (VATS). Pathologic examination of lung biopsy showed nonspecific interstitial pneumonitis (NSIP) pattern. Differential diagnosis of NSIP pattern includes: pneumonitis secondary to autoimmune disorders, inhalation-induced lung injury, drug reactions, and hypersensitivity pneumonitis. Detailed history, physical examination, and extensive laboratory investigation excluded hypersensitivity pneumonitis and autoimmune-related ILD. Idiopathic interstitial pneumonitis with NSIP pattern is a rare entity and although idiopathic NSIP can not be excluded, we believe clinical course, symptoms, and pathologic findings can be best explained by exposure and inhalation of toxic components of the airbag. Frontal airbags are held to have saved almost 14,000 lives between 1987 and 2003. Airbags on both the driver and passenger sides have been required in all new cars manufactured after September 1997. In purely frontal crashes, airbags reduce the fatality risk by 34%. Nevertheless, several different types of injury are attributed to airbag deployment and, occasionally, to its rupture. Asthmatic reactions, reactive airway dysfunction syndrome (RADS) due to sodium azide (propellant for the inflation of airbags) inhalation, and bilateral pneumothorax in the absence of associated chest trauma have been reported as a consequence of airbag deployment and/or rupture. To the best of our knowledge, however, there are no reported cases of parenchymal lung disease associated with airbag deployment and/or rupture. Automobile airbags are designed to inflate upon sudden deceleration. The bag itself is made of a thin, nylon fabric that is folded into the steering wheel or dashboard. When there is a collision force equal to running into a brick wall at 10

High Resolution Computed Tomography of Bleomycin-Induced Lung Injury in Hodgkin Lymphoma.

Bleomycin is the chemotherapeutic agent most commonly associated with pulmonary toxicity in about 4–20% of treated patients. The diagnosis of bleomycin-induced lung disease is primarily clinical and there is no true gold standart test available. In this study, we aimed to evaluate the role of high resolution computed tomography (HRCT) in monitoring patients for drug toxicity.We prospectively evaluated the HRCT scans of 18 newly diagnosed hodgkin lymphoma patients baseline, after the fourth and the eight cycle of ABVD (Adriamycin-bleomycin-vinblastine-dacarbazine) chemotherapy. The age ranges of the patients was 17–69 years (mean, 35 years). Serial PFTs and arterial blood gases were obtained in addition to imaging studies during bleomycin therapy. The parenchymal abnormalities on HRCT were grouped into different categories according to the dominant pattern and distribution of disease: diffuse alveolar damage (DAD), nonspecific interstitial pneumonitis (NSIP), bronchiolitis obliterans organizing pneumonia (BOOP), interstitial pneumonitis and fibrosis and hypersensitivity reaction. Pulmonary parenchymal abnormalities were detected on HRCT in 5 of 18 patients (27.8%). Patient details, cumulative doses of bleomycin and patterns of lung injury are presented in table. Arterial O2 pressure (p<0.01), O2 saturation (p<0.01) and carbon monoxide diffusing capacity (DLCO) (p<0.01) were decreased after bleomycin therapy compared to baseline values in 18 patients.Our results indicate that HRCT is useful in the diagnosis of bleomycin-induced lung disease by better characterization of the nature of the abnormality and assessment of extent and distribution of disease.Bleomycin-induced lung diseaseNoAgeSexDosePattern of lung injury146M234 mgBOOP230M128 mgNSIP369F210 mgNSIP426M162 mgBOOP551M256 mgNSIP

Hydroxychloroquine and Surfactant Protein C Deficiency

To the Editor: We wish to report initial success in treating a boy with surfactant protein C deficiency. The patient was first admitted to the hospital at five months of age with severe respiratory distress that followed a viral respiratory infection. Open-lung biopsy revealed nonspecific interstitial pneumonitis, and DNA analysis revealed that the gene encoding surfactant protein C had a C-to-A substitution leading to an alanine-to-aspartate substitution at amino acid 116 in exon 4. The patient was discharged home in moderate respiratory distress; he was breathing oxygen at a rate of 2 to 3 liters per minute by nasal cannula . . .

Increased CD4+ T cell infiltrates in rheumatoid arthritis–associated interstitial pneumonitis compared with idiopathic interstitial pneumonitis

To study lymphocyte markers in rheumatoid arthritis (RA)-associated interstitial pneumonitis (IP) compared with idiopathic IP. Paraffin-embedded lung biopsy specimens from patients with RA (n = 15) and from those without RA (n = 16), all of whom had a diagnosis of either nonspecific IP or usual IP, were studied. Tissue sections from each patient were reviewed by a pathologist, who was blinded to the clinical data. Age and pulmonary function test results were similar in RA and non-RA patients. After high-temperature antigen unmasking, sections were incubated with mouse monoclonal antibodies directed against CD3, CD4, CD8, CD16, and CD20. All slides were coded, and digital images (100x magnification) of the entire tissue area were obtained. Staining was quantified using computer-assisted image analysis. Staining for CD4 was more prominent in patients with RA than in the non-RA comparison group (median 9.3 cells/mm(2), interquartile range [IQR] 5.5-27.3 versus 0.6 cells/mm(2), IQR 0.2-1.9; P = 0.002). CD4+ cell counts were increased in RA patients with nonspecific IP as well as in RA patients with usual IP, with no major difference between these groups. Results were similar for quantification of CD3 (P = 0.012). There was a less striking trend toward more CD8+ cells in RA patients (P = 0.27 versus those with non-RA lung disease). IP lesions in patients with RA are characterized by an increased number of CD4+ cells, as compared with that in patients with idiopathic IP. This finding suggests that CD4+ T cells are critical for the development of pulmonary manifestations in RA, and may have implications for the treatment of RA-associated lung disease.

Familial Interstitial Lung Disease in Two Young Korean Sisters

Most of the interstitial lung diseases are rare, chronic, progressive and fatal disorders, especially in familial form. The etiology of the majority of interstitial lung disease is still unknown. Host susceptibility, genetic and environmental factors may influence clinical expression of each disease. With familial interstitial lung diseases, mutations of surfactant protein B and surfactant protein C or other additional genetic mechanisms (e.g. mutation of the gene for ATP-binding cassette transporter A3) could be associated. We found a 21 month-old girl with respiratory symptoms, abnormal radiographic findings and abnormal open lung biopsy findings compatible with nonspecific interstitial pneumonitis that is similar to those of her older sister died from this disease. We performed genetic studies of the patient and her parents, but we could not find any mutation in our case. High-dose intravenous methylprednisolone and oral hydroxychloroquine were administered and she is still alive without progression during 21 months of follow-up.