Features Of Nonspecific Interstitial Pneumonia Research Articles

DYSPNEA UNVEILED BY HANDS: A CHALLENGING CASE OF RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASE

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Antisynthetase syndrome (ASS) is a rare autoimmune condition characterized by antibodies directed against amino-acyl-tRNA synthetase along with clinical features of myositis, arthritis, Raynaud’s phenomenon and interstitial lung disease (ILD). We present a case of rapidly progressive ASS associated ILD. CASE PRESENTATION: A 40-year-old African American woman with past medical history of smoking and prior hospitalization for presumed pneumonia presented to the emergency department with complaints of ongoing but worsening cough and dyspnea for more than four months. She was hypoxic and lung examination revealed bilateral fine crackles. Chest imaging revealed patchy mixed consolidation and ground-glass opacities at the lung bases (figure 1). Her course worsened needing mechanical ventilation. Given the clinical picture and imaging findings raising concerns for ILD, she underwent VATS/lung biopsy, which revealed pinkish fibrous plugs: Masson bodies, concerning for organizing pneumonia (figure 2). Autoimmune work including ANA and rheumatoid factor was negative. She continued to decline despite broad-spectrum antibiotics and high dose steroids and had to be placed on VV-ECMO for severe ARDS. Hyperkeratosis and hyperpigmentation of her hands were later noted, raising concerns for an autoimmune process. A myositis panel was done, which revealed positive Anti-PL12 antibodies. Lung function recovery was sub-optimal despite ECMO support for 85 days, IVIG, plasma exchange and cyclophosphamide therapy. She had to undergo single left lung transplantation. She eventually was discharged home on immunosuppressants after five months of hospitalization. Her explanted lung showed features of non-specific interstitial pneumonia. She has done well for more than 2 years post-transplant with amelioration in the imaging findings of her native right lung and with no signs of graft rejection. The final diagnosis was rapidly progressive ASS associated ILD with progression to ARDS requiring single lung transplantation. DISCUSSION: ASS is a rare group of idiopathic inflammatory myopathies, characterized by the presence of seven different myositis-specific antisynthetase antibodies with Anti-Jo1 being the most common one. Anti-PL12 antibody type is associated with a severe form of ILD. ANA antibodies are typically negative and hence a high index of suspicion for ASS is warranted. Literature about the management of ASS-ILD is sparse but anecdotal experience favors steroids as first-choice agents and other immunosuppressive agents, plasma exchange therapy, and even lung transplantation in severe and refractory cases. CONCLUSIONS: Our case of ASS-ILD with anti-PL12 antibodies shows the rapid progression of the ILD despite aggressive immunosuppressive therapy and highlights the importance of identification, aggressive therapy and the role of VV-ECMO with lung transplantation as an option for refractory cases. Reference #1: Connors GR, Christopher-Stine L, Oddis CV, et al. Interstitial lung disease associated with the idiopathic inflammatory myopathies: what progress has been made in the past 35 years? Chest. 2010;138:1464–1474. Reference #2: Esposito AC, Gige TC, Miot HA. Syndrome in question: antisynthetase syndrome (anti-PL-7). An Bras Dermatol. 2016;91(5):683-685. DOI:10.1590/abd1806-4841.20164449 Reference #3: Witt LJ, Curran JJ, Strek ME. The Diagnosis and Treatment of Antisynthetase Syndrome. Clin Pulm Med. 2016;23(5):218-226. DOI:10.1097/CPM.0000000000000171 DISCLOSURES: No relevant relationships by Anas Alameh, source=Web Response No relevant relationships by Ansaam Daoud, source=Web Response No relevant relationships by Sujith Modugula, source=Web Response No relevant relationships by Lokesh Venkateshaiah, source=Web Response No relevant relationships by Elizabeth Verghese, source=Web Response

Organizing pneumonia components in non-specific interstitial pneumonia (NSIP): a clinicopathological study of 33 NSIP cases.

To review the clinical, radiological and pathological features of non-specific interstitial pneumonia (NSIP), mainly to characterize organizing pneumonia (OP) components in NSIP. Lung biopsy samples from 33 NSIP patients were collected over a period of 10years. Microscopic analysis revealed that 13 cases showed a cellular pattern and 20 showed a mixed/fibrosing pattern. OP components were detected in 26 cases (13 with a cellular pattern; 13 with a mixed/fibrosing pattern), and were found to constitute a median proportion of 9% (range, 1-40%) of the affected tissues. In nine cellular and four mixed/fibrosing NSIP cases, the OP components accounted for ≥10%. A proportion of ≥20% was found in only five cellular pattern cases. Twenty-nine patients were followed up: 17 showed improvements, five were stabilized, and seven showed progression. OP components are common basic lesions in NSIP cases, although their proportion in cellular and mixed/fibrosing pattern cases varies substantially between patients. OP components do not impact on prognosis, even when they constitute ≥20% of the affected tissue. Thus, a high level of OP components does not exclude a diagnosis of NSIP in cases that otherwise show pathological and radiological findings characteristic of NSIP.

P22 Endoplasmic Reticulum Stress Markers Correlate With Fibrosis In Idiopathic Pulmonary Fibrosis And Non-specific Interstitial Pneumonia

Idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) are forms of idiopathic interstitial pneumonias that have distinct histopathological features and outcomes. It is unknown if these idiopathic interstitial pneumonias have common mechanisms of fibrosis. Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of sporadic and familial idiopathic pulmonary fibrosis. In response to endoplasmic reticulum (ER) stress, cells trigger the unfolded protein response (UPR) with upregulation of chaperones, such as BiP, and the phosphatase growth arrest and DNA damage 34 (GADD34). However, this may have profound effects on cell proliferation and survival. We hypothesised that ER stress may also be involved in the pathogenesis of NSIP. Paraffin embedded lung biopsy sections from 4 patients with sporadic idiopathic pulmonary fibrosis (IPF) (UIP histopathology) and 4 non-specific interstitial pneumonia (NSIP) (NSIP histopathology) were evaluated for the ER stress markers BiP and GADD34 using immunohistochemistry. For each biopsy sample, six high power fields (x 200 magnification) were scored for fibrosis and inflammation as well as BiP and GADD34 using semi-quantitative analysis by 2 blinded, independent investigators. BiP and GADD34 were expressed in areas of fibrosis, localised to reactive type II pneumocytes and endothelial cells. No staining was detected in fibroblasts or fibroblastic foci. In sporadic IPF (UIP), levels of BiP within the epithelium correlated with fibrosis (r 2 0.56, p = 0.0001, Figure 1a) more than inflammation (r 2 0.38, p = 0.0013). In contrast, epithelial GADD34 was more strongly associated with NSIP fibrosis (r 2 0.56, p These data suggest that ER stress and the unfolded protein response are features of NSIP as well as IPF and may play a role in determining the severity of the fibrotic response.

FRI0518 A Loss of Telocytes Accompanies Fibrosis of Multiple Organs in Systemic Sclerosis

BackgroundTelocytes are a distinct population of stromal (interstitial) cells recently identified in a variety of tissues and organs. By their extremely long cytoplasmic processes telocytes form a three-dimensional network that...

OP0222 Inactivation of Urokinase-Type Plasminogen Activator Receptor Induces Dermal and Pulmonary Fibrosis and Peripheral Microvasculopathy in Mice Closely Resembling Human Systemic Sclerosis

BackgroundUrokinase-type plasminogen activator receptor (uPAR) is a key component of the fibrinolytic system which plays an important role in the degradation of the extracellular matrix (ECM). uPAR concentrates the serine...

The Histopathology of Idiopathic Pulmonary Fibrosis in West Highland White Terriers Shares Features of Both Non-specific Interstitial Pneumonia and Usual Interstitial Pneumonia in Man

Idiopathic pulmonary fibrosis (IPF) in West Highland white terriers (WHWTs) is a breed-related, spontaneously arising disease that is a potential animal model for IPF in man. Histopathological similarity between IPF in WHWTs and usual interstitial pneumonia (UIP), the histopathological correlate for IPF in man, has not been confirmed and histological features of non-specific interstitial pneumonia (NSIP), another form of human idiopathic interstitial pneumonia, have been reported in WHWTs with IPF. This study describes the pulmonary histopathological findings in 18 WHWTs with IPF, including lobe-specific samples in nine of the dogs. The canine lesions and their distribution pattern are compared with histopathological characteristics in samples of human UIP and NSIP. Underlying diffuse mature fibrosis, resembling human NSIP more than UIP, was seen in the lungs of all dogs with IPF. Additionally, the majority of dogs with IPF showed multifocal areas of accentuated subpleural and peribronchiolar fibrosis with occasional 'honeycombing' and profound alveolar epithelial changes, reminiscent of human UIP and not commonly seen in NSIP. Interstitial fibroblastic foci, characteristic of UIP, were not seen in WHWTs with IPF. Progressive fibrosis, with intra-alveolar organizing fibrosis alongside interstitial mature collagen deposition, was present within the more severely affected areas of lung in WHWTs with IPF. Severe pulmonary lesions were seen more commonly in the caudal than in the cranial lung lobes.

Histological features of nonspecific interstitial pneumonia

Nonspecific interstitial pneumonia is a type of idiopathic interstitial pneumonia. By definition, the cases of nonspecific interstitial pneumonia are those which cannot be classified as any other type of interstitial pneumonia. The Material of the investigation included 12 transbronchial biopsy lung samples. The quantity, structure and distribution of specific cellular elements were determined semiquantitatively, recognizing three levels of the lesions' intensity: mild/ poor, moderate, and intense/abundant. The interalveolar septa were most frequently moderately thickened (50% of the cases) due to the presence of inflammatory cells and multiplied connective. Of the inflammatory cells, lymphocytes were most common and greatest in quantity (abundant, moderate and poor in 4, 5, and 3 cases respectively), followed by plasma cells and macrophages. The septal connective was moderately and mildly multiplied in 2 and 4 cases respectively. The lumen of the alveoli was infiltrated by lymphocytes and macrophages, while poor peribronchial and perivascular lymphocyte infiltrates were most commonly found. The interalveolar septa were most frequently moderately thickened due to the presence of chronic inflammatory cells, predominantly lymphocytes, as well as to mildly-to-moderately multiplied connective. The lymphocytes usually permeated the septa diffusely. Bronchiolar and blood vessel findings were nonspecific.

Quantitative comparison of idiopathic interstitial pneumonias on high-resolution computed tomographic findings

To analyze the high-resolution computed tomographic (HRCT) findings of IPF (interstitial pulmonary fibrosis), NSIP (nonspecific interstitial pneumonia) and COP (cryptogenic organizing pneumonia) retrospectively through quantification methods and to explore their distinguishing features. Observers with no prior knowledge of the diagnosis evaluated the frequency, extent and distribution of various thin-section CT findings in 29 males and 17 females. The mean age was 50 ± 10 years old (range: 25 - 76). They had a histological diagnosis of IPF (n = 19), nonspecific interstitial pneumonia (NSIP) (n = 14) and cryptogenic organizing pneumonia (COP) (n = 13). Ground-glass opacity, thickening of bronchovascular bundles and interlobular septal thickening were frequent features of IPF and NSIP. The frequency and extent of honeycombing and bronchiolectasis were more found in IPF than in NSIP and COP (P < 0.05). The frequency and extent of air space consolidation were more found in COP than IPF (P < 0.05). There were more number of segments with traction bronchiectasis and less extent of air space consolidation in IPF than NSIP and COP. The number of segments with traction bronchiectasis was less in NSIP than that of IPF and COP. The various subtypes of idiopathic interstitial pneumonias often have the distinguishing characteristics easily identified on HRCT. Bronchiolectasis and honeycombing are valuable features for IPF; air space consolidation is a valuable feature for COP. The features of NSIP are also found in both IPF and COP so that additional features are required for both.

High-Resolution Computed Tomography Features of Nonspecific Interstitial Pneumonia and Usual Interstitial Pneumonia

High-Resolution Computed Tomography Features of Nonspecific Interstitial Pneumonia and Usual Interstitial Pneumonia

High-Resolution Computed Tomography Features of Nonspecific Interstitial Pneumonia and Usual Interstitial Pneumonia

To assess the accuracy of high-resolution computed tomography (HRCT) in the diagnosis of nonspecific interstitial pneumonia (NSIP). We hypothesized that the computed tomography (CT) features of NSIP could be distinguished from those of usual interstitial pneumonia (UIP). The HRCT images of 47 patients with surgical lung biopsy-proven NSIP (n = 25) and UIP (n = 22) were independently reviewed by 2 thoracic radiologists. Predominant imaging patterns, most likely diagnosis, and diagnostic level of confidence were recorded. A confident HRCT diagnosis of NSIP was based on the presence of spatially uniform, bilateral, basal-predominant ground-glass and/or reticular opacities with little if any honeycombing, whereas UIP was confidently diagnosed if a spatially inhomogeneous, bilateral, peripheral, basal-predominant pattern of reticular opacities and honeycombing with little if any ground-glass attenuation was identified. A predominant pattern of ground-glass and/or reticular opacity with minimal to no honeycombing was demonstrated in 48 (96%) of 50 readings in patients with NSIP. Conversely, the presence of honeycombing as a predominant feature had a predictive value of 90% for UIP (P < 0.001). Usual interstitial pneumonia was more likely than NSIP to be subpleural and patchy (P < 0.001). A confident CT diagnosis of NSIP and UIP was correct in 73% and 88% of cases, respectively. The correctness of a CT diagnosis made at intermediate or high confidence was 68% and 88%, respectively. The kappa value for distinction of NSIP from UIP was 0.72. In contrast to previous reports, NSIP can be separated from UIP in most cases. The presence of honeycombing as a predominant imaging finding is highly specific for UIP and can be used to differentiate it from NSIP, particularly when the distribution is patchy and subpleural predominant. The presence of predominant ground-glass and reticular opacity is highly characteristic of NSIP, but there is a subset of patients with UIP who have this pattern and may require biopsy for differentiation from NSIP.

Fibrotic Idiopathic Interstitial Pneumonia: High-Resolution Computed Tomography Considerations

The fibrotic idiopathic interstitial pneumonias comprise usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). The characteristic high-resolution computed tomography findings of UIP are reticular abnormality and honeycombing with basal and peripheral predominance. Honeycombing is the strongest predictor of UIP. The extent of fibrosis on computed tomography (CT) is an important prognostic indicator in idiopathic pulmonary fibrosis (IPF). When ground-glass attenuation is seen in IPF it commonly progresses to fibrosis and honeycombing. Imaging may help to detect complications of IPF, including accelerated progression, lung cancer, and secondary infection. Our understanding of the clinical and radiological features of NSIP is still evolving. The CT finding of extensive ground-glass abnormality and some reticular abnormality, with basal and peripheral predominance, is strongly suggestive of NSIP. However, the CT appearances of NSIP overlap with those of UIP, organizing pneumonia (OP), and desquamative interstitial pneumonia (DIP), and biopsy may be necessary to sort this out. Other idiopathic pneumonias that may be associated with CT evidence of lung fibrosis include DIP, OP, acute interstitial pneumonia, and lymphoid interstitial pneumonia.

Clinical features of non-specific interstitial pneumonia

The clinical features of 24 patients with non-specific interstitial pneumonia (NIP) were evaluated. The patients consisted of seven men and 17 women, with a median age of 60 years. In seven patients, the disease was idiopathic and eight had collagen vascular diseases. Cough, dyspnoea and fever were frequently observed. The time interval between the onset of symptoms and open lung biopsy was 3 months. Mild increases of IgG, CRP, and LDH were also frequently observed. The average per cent VC was 65·1 ± 3·2% and the average PaO 2 was 71·3 ± 2·4 Torr. Bronchoalveolar lavage was done in 20 patients, and a moderate increase in lymphocytes (27·8 ± 6·7%) with a low CD4 CD8 ratio (0·86 ± 0·22) was observed. Multiple patchy infiltration or diffuse interstitial shadows, located predominantly in the lower fields of both lungs were the characteristic chest CT findings. Lung biopsies in this group were characterized by varying proportions of chronic interstitial inflammation and fibrosis which was temporarily uniform. Patients were given steroid pulse therapy or oral steroids. The results were mild to marked improvements in chest roentgenographic findings and lung functions. Four patients (16·7%) died because of respiratory failure caused by NIP. This is the first report to describe clinical features of NIP since the original report by Katzenstein and Fiorelli.