Nonspecific Interstitial Pneumonia Patients Research Articles

Clinical behaviour and mortality in idiopathic vs secondary nonspecific interstitial pneumonia.

Nonspecific interstitial pneumonia (NSIP) is a subtype of interstitial lung disease which can either be idiopathic or secondary to other conditions. Idiopathic NSIP is a relatively rare entity and diagnosis should be considered carefully as it is mainly a diagnosis of exclusion. The aim of this retrospective study was to evaluate a cohort of NSIP patients with a view to identifying any clinical and mortality differences between idiopathic and secondary varieties. We screened 700 patients from our interstitial lung disease database and identified 44 cases of NSIP retrospectively. Statistical analysis was conducted to evaluate if there was a difference in demographics such as gender and ethnicity, physiological parameters including forced vital capacity, diffusing capacity, average oxygen saturations, and immunology profile between two groups. Furthermore, a difference in mortality was evaluated between idiopathic and secondary NSIP. The data analysis showed that 63.6% (28 of 44) of patients had idiopathic NSIP versus 36.4% (16 of 44) of patients had secondary NSIP. Majority of the secondary NSIP patients had an underlying connective tissue disease. In the idiopathic variety, there was a male preponderance (64.2%, P = .02) which was statistically different compared to relatively equal gender divide in secondary NSIP which was statistically insignificant (male vs. female: 43.8% vs. 56.3%, respectively, P = .42). The mean age of the idiopathic group was 74 years compared to 64 years in the secondary group which was statistically different (P = .01). In both groups (idiopathic and secondary NSIP), more than two-thirds (68%) were of White British ethnicity. Immunology profile was similar across both groups with no statistical difference in IgM, IgG, or IgA levels. At the time of analysis, there were 17.9% deaths (5 of 28) in the idiopathic NSIP group versus 6.3% (1 of 16) in the secondary NSIP group but this was not statistically significant (P = .14). Similarly, there was no statistically significant difference in the forced vital capacity (P = .59), diffusing capacity (P = .88), and resting oxygen saturations (P = .28) between idiopathic and secondary NSIP varieties. Our analysis showed that there was a statistically significant difference in gender (male preponderance in idiopathic NSIP only) and mean age difference among both varieties. There were no statistically significant differences in the clinical features and outcomes including mortality, physiological, and immunological parameters between idiopathic and secondary NSIP. Idiopathic NSIP was more common than secondary NSIP and secondary NSIP is mostly due to underlying connective tissue disease.

Histologic Analysis of Idiopathic Pulmonary Fibrosis by Morphometric and Fractal Analysis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disorder, ultimately leading to respiratory failure and death. Despite great research advances in understanding the mechanisms underlying the disease, its diagnosis, and its treatment, IPF still remains idiopathic without known biological or histological markers able to predict disease progression or response to treatment. The histologic hallmark of IPF is usual interstitial pneumonia (UIP), with its intricate architectural distortion and temporal inhomogeneity. We hypothesize that normal lung alveolar architecture can be compared to fractals, such as the Pythagoras tree with its fractal dimension (Df), and every pathological insult, distorting the normal lung structure, could result in Df variations. In this study, we aimed to assess the UIP histologic fractal dimension in relationship to other morphometric parameters in newly diagnosed IPF patients and its possible role in the prognostic stratification of the disease. Clinical data and lung tissue specimens were obtained from twelve patients with IPF, twelve patients with non-specific interstitial pneumonia (NSIP), and age-matched "healthy" control lung tissue from patients undergoing lung surgery for other causes. Histology and histomorphometry were performed to evaluate Df and lacunarity measures, using the box counting method on the FracLac ImageJ plugin. The results showed that Df was significantly higher in IPF patients compared to controls and fibrotic NSIP patients, indicating greater architectural distortion in IPF. Additionally, high Df values were associated with higher fibroblastic foci density and worse prognostic outcomes in IPF, suggesting that Df may serve as a potential novel prognostic marker for IPF. The scalability of Df measurements was demonstrated through repeated measurements on smaller portions from the same surgical biopsies, which were selected to mimic a cryobiopsy. Our study provides further evidence to support the use of fractal morphometry as a tool for quantifying and determining lung tissue remodeling in IPF, and we demonstrated a significant correlation between histological and radiological Df in UIP pattern, as well as a significant association between Df and FF density. Furthermore, our study demonstrates the scalability and self-similarity of Df measurements across different biopsy types, including surgical and smaller specimens.

Prevalence of myositis specific and associated antibodies in a cohort of patients affected by idiopathic NSIP and no hint of inflammatory myopathies.

The presence of interstitial lung disease (ILD) is a common and fearsome feature of idiopathic inflammatory myopathies (IIM). Such patients show radiological pattern of non-specific interstitial pneumonia (NSIP). The present study aimed to assess the prevalence of myositis-specific and myositis-associated antibodies (MSA and MAA) in a cohort of patients with a previous diagnosis of NSIP and no sign or symptom of IIM. Secondly, it will be assessed whether patients displaying MSA and/or MAA positivity have a worse or a better outcome than idiopathic NSIP. All patients affected by idiopathic NSIP were enrolled. MSA and MAA were detected using EUROLINE Autoimmune Inflammatory Myopathies 20 Ag (Euroimmun Lubeck, Germany), line immunoassay. A total of 16 patients (mean age 72 ± 6.1years old) were enrolled. Six out of 16 patients (37.5%) had significant MSA and/or MAA positivity: one displayed positivity of anti-PL-7 (+ +), one of anti-Zo (+ +), anti-TIF1γ (+ + +) and anti-Pm-Scl 75 (+ + +), one of anti-Ro52 (+ +), one of anti-Mi2β (+ + +), one of anti-Pm-Scl 75 (+ + +) and the latter of both anti-EJ (+ + +) and anti-Ro52 (+ + +).Two out of 7 seropositive patients showed a significant impairment of FVC (relative risk 4.8, 95% CI 0.78-29.5; p = 0.0350). Accordingly, among the 5 patients that started antifibrotic treatment during the observation time, 4 were seronegative. Our findings highlighted a potential autoimmune or inflammatory in idiopathic NSIP patients and also in those without significant rheumatological symptoms. A more accurate diagnostic assessment may ameliorate diagnostic accuracy as well as may provide new therapeutic strategy (antifibrotic + immunosuppressive). A cautious assessment of NSIP patients with a progressive and non-responsive to glucocorticoids disease course should therefore include an autoimmunity panel comprising MSA and MAA.

New York Heart Association class and pulmonary artery pressure as prognostic factors of interstitial lung disease survival.

The aim of this study was to evaluate New York Heart Association (NYHA) class and systolic pulmonary artery pressure (sPAP) as survival predictors in major interstitial lung diseases (ILD) including idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP) and hypersensitivity pneumonitis (HP) and in other ILD like granulomatosis with polyangiitis (GPA). We analyzed survival, NYHA class, sPAP, and Octreoscan uptake index (UI) in 104 ILD patients (59 IPF, 19 NSIP, 10 HP and 16 GPA; median age 60.5 years) all referred to a single centre. Median survival was 68 months, with 1- and 2-year survival of 91% and 78%, respectively. Survival was lower among IPF and NSIP vs. HP and GPA patients (p=0.01). NYHA class 3-4 was more frequent among IPF (76.3%) vs. NSIP patients (31.6%; p<0.001). HP and GPA had NYHA class 1-2. NYHA class was negatively associated with survival (class 1=90.3 months vs. class 3=18.3 months and class 4=5.1 months; p=0.001). sPAP was >55 mmHg in 76.3% of patients with IPF and 35-55 mmHg in 63.2% of patients with NSIP. Patients with HP and GPA had sPAP < 55 mmHg. Among patients with IPF, NYHA and sPAP were negatively associated with survival (p<0.01) both showed a parallel trend. High-resolution computed tomography and survival were worse among IPF and NSIP vs. HP and GPA patients (p<0.001). Octreoscan UI was <10, 10-12, and >12 in IPF, NSIP, HP and GPA, respectively. Octreoscan UI was negatively associated with survival (p=0.002). NYHA class and sPAP are comparable ILD survival predictors. NYHA class is correlated with worse prognosis for IPF and NSIP vs. HP and GPA patients.

Pulmonary vessel volume can help to differentiate fibrotic lung diseases

Objectives: Idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP), and chronic hypersensitivity pneumonitis (CHP) are diffuse fibrosing lung diseases that are sometimes difficult to differentiate by only visual evaluation of CT images. We aimed to find if pulmonary vessel volume (PVV), a new quantitative CT measure, can help to differentiate these diseases at the time of diagnosis. Methods: We retrospectively measured PVV values of IPF, NSIP, and CHP patients diagnosed within the last five years in our institution, by using their CT images at the time of diagnosis. We used CALIPER-technology (Computer-Aided Lung Informatics for Pathology Evaluation and Rating) for the quantification of CT images. We compared the PVV values of disease groups by the Kruskal-Wallis test and performed ROC curve analysis to evaluate the ability of PVV to differentiate these diseases. Results: We measured the PVV values of 152 patients, 113 of them were diagnosed with IPF, 16 with NSIP, and 23 with CHP. The PVV value of the NSIP group was significantly lower than that of both IPF (p = 0.028) and CHP (p = 0.013) groups. However, there was no significant difference between IPF and CHP groups (p = 0.924). Selected cut-off values of PVV were found to differentiate NSIP from IPF with a specificity of 88%, and NSIP from CHP with a specificity of 91%. Conclusions: PVV measured by CALIPER at the time of diagnosis can help to differentiate NSIP from both IPF and CHP.

Galactin-1, 3 and 9: Potential biomarkers in idiopathic pulmonary fibrosis and other interstitial lung diseases

IntroductionGalectins are proteins that bind β-galactosides such as N-acetylactosamine present in N-linked and O-linked glycoproteins and that seem to be implicated fibrotic mechanisms. Here we aimed to define the role of serum galectins in idiopathic pulmonary fibrosis and idiopathic non-specific interstitial pneumonia (NSIP) by comparison with other chronic interstitial lung diseases (ILDs) and healthy subjects. MethodsForty-one fibrotic ILD patients (median age (IQR), 65 years (20); 50 % male) were enrolled in the study. Peripheral blood concentrations of galectins-1, 3 and 9 were determined with commercial ELISA kits. ResultsGalectin-1 and 9 concentrations were higher in the ILD group than in healthy controls (p = 0.0318 and p < 0.0001, respectively). Galectin-3 was also higher in ILD patients (borderline significant p = 0.0617). In particular, significantly higher Gal-1 concentrations were found in sarcoidosis and NSIP patients (p = 0.0418 and p = 0.0015, respectively), while Gal-9 concentrations were significantly higher in all ILD subgroups. Specific cut-offs for all galectins were calculated by receiver operating curve (ROC) analysis. Several correlations with lung function parameters were found. DiscussionGalectins 1, 3 and 9 concentrations were found altered in serum of ILD patients suggesting their potential utility as clinical, diagnostic and prognostic biomarkers. Inhibition of galectins may be useful in the therapeutic management of pulmonary fibrosis. Further studies on larger case series would be worthwhile.

Non-specific interstitial pneumonia and features of connective tissue disease: What are the consequences of a different point of view?

Patients with Interstitial Lung Disease (ILD) without a definitive diagnosis of connective tissue diseases (CTD) were historically described as Undifferentiated Connective Tissue Disease (UCTD-ILD). Recently a new classification, Interstitial Pneumonia with Autoimmune Features (IPAF), has been proposed. Aim of this study was to describe the prevalence, clinical characteristics and prognostic factors of UCTD and IPAF subjects in a cohort of Non-Specific Interstitial Pneumonia (NSIP) patients. This retrospective, observational study enrolled 102 adult patients characterized by NSIP pattern on High Resolution Computed Tomography, without a specific diagnosis of CTD. Three groups were identified according to patients' characteristics: IPAF, UCTD or idiopathic NSIP (iNSIP). Forty percent, 27% and 55% of patients showed diagnostic criteria for IPAF, UCTD and iNSIP, respectively. No significant differences in age, gender, smoking habit, pulmonary function tests and three-year survival rate were observed among study groups. IPAF patients with antisynthetase antibodies positivity, in comparison to IPAF without antisynthetase antibodies positivity, showed more frequently an acute onset (44% vs 9%, p<0.012). The presence of autoimmune features seems not to be associated with better outcomes in NSIP patients. IPAF criteria seem to be more representative than UCTD criteria in identifying patients with autoimmune features. Further studies are needed to verify if IPAF should include patients with positive antisynthetase serology.

Distinctive characteristics and prognostic significance of interstitial pneumonia with autoimmune features in patients with chronic fibrosing interstitial pneumonia.

Interstitial lung diseases are heterogeneous, and patients with chronic fibrosing interstitial pneumonia (CFIP) often have clinical, serologic, and morphologic features suggestive but not diagnostic of connective tissue disease. Recently, the concept of interstitial pneumonia with autoimmune features (IPAF) has been proposed as a platform for such patients. However, the prognostic role of IPAF, including the cumulative incidence of acute exacerbations (AEs), is not fully clear. The aim of this study was to elucidate the clinical features and prognostic significance of IPAF. The clinical characteristics and prognostic relevance of a diagnosis of IPAF were retrospectively explored in 194 patients with CFIP, including 163 with idiopathic pulmonary fibrosis (IPF) and 31 with nonspecific interstitial pneumonia (NSIP), in our interstitial lung disease database. Sixteen percent of patients with CFIP (8% of IPF, 61% of NSIP) met the criteria for IPAF. Patients with IPAF were significantly younger and included a higher proportion of women, never-smokers, and patients with NSIP than those without IPAF. The morphologic domain was the most common in patients with IPAF (97%), followed by the serologic domain (72%) and clinical domain (53%). CFIP patients with IPAF had a more favorable prognosis with regard to overall survival (OS; P < 0.001, log-rank test) and incidence of AEs (P = 0.029, Gray's test) than those without IPAF. In the subgroup analysis, NSIP patients with IPAF had significantly better survival than those without IPAF (P = 0.031, log-rank test), and IPF patients with IPAF tended to have better OS than those without IPAF (P = 0.092, log-rank test). However, there were no significant differences in the incidence of AEs between patients with IPAF and those without IPAF in the IPF and NSIP subgroups. Furthermore, fulfilment of the IPAF criteria was an independent predictor of OS (hazard ratio (HR) 0.127; 95% confidence interval (CI) 0.017-0.952; P = 0.045) and incidence of AEs (HR 0.225: 95% CI 0.054-0.937; P = 0.040). A diagnosis of IPAF might predict a favorable prognosis and less risk of AEs in patients with CFIP.

Short-term Automated Quantification of Radiologic Changes in the Characterization of Idiopathic Pulmonary Fibrosis Versus Nonspecific Interstitial Pneumonia and Prediction of Long-term Survival.

Fibrotic interstitial lung diseases presenting with nonspecific and overlapping radiologic findings may be difficult to diagnose without surgical biopsy. We hypothesized that baseline quantifiable radiologic features and their short-term interval change may be predictive of underlying histologic diagnosis as well as long-term survival in idiopathic pulmonary fibrosis (IPF) presenting without honeycombing versus nonspecific interstitial pneumonia (NSIP). Forty biopsy-confirmed IPF and 20 biopsy-confirmed NSIP patients with available high-resolution chest computed tomography 4 to 24 months apart were studied. CALIPER software was used for the automated characterization and quantification of radiologic findings. IPF subjects were older (66 vs. 48; P<0.0001) with lower diffusion capacity for carbon monoxide and higher volumes of baseline reticulation (193 vs. 83 mL; P<0.0001). Over the interval period, compared with NSIP, IPF patients experienced greater functional decline (forced vital capacity, -6.3% vs. -1.7%; P=0.02) and radiologic progression, as noted by greater increase in reticulation volume (24 vs. 1.74 mL; P=0.048), and decrease in normal (-220 vs. -37.7 mL; P=0.045) and total lung volumes (-198 vs. 58.1 mL; P=0.03). Older age, male gender, higher reticulation volumes at baseline, and greater interval decrease in normal lung volumes were predictive of IPF. Both baseline and short-term changes in quantitative radiologic findings were predictive of mortality. Baseline quantitative radiologic findings and assessment of short-term disease progression may help characterize underlying IPF versus NSIP in those with difficult to differentiate clinicoradiologic presentations. Our study supports the possible utility of assessing serial quantifiable high-resolution chest computed tomographic findings for disease differentiation in these 2 entities.

Development of a Computer-Aided Differential Diagnosis System to Distinguish Between Usual Interstitial Pneumonia and Non-specific Interstitial Pneumonia Using Texture- and Shape-Based Hierarchical Classifiers on HRCT Images.

A computer-aided differential diagnosis (CADD) system that distinguishes between usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) using high-resolution computed tomography (HRCT) images was developed, and its results compared against the decision of a radiologist. Six local interstitial lung disease patterns in the images were determined, and 900 typical regions of interest were marked by an experienced radiologist. A support vector machine classifier was used to train and label the regions of interest of the lung parenchyma based on the texture and shape characteristics. Based on the regional classifications of the entire lung using HRCT, the distributions and extents of the six regional patterns were characterized through their CADD features. The disease division index of every area fraction combination and the asymmetric index between the left and right lungs were also evaluated. A second SVM classifier was employed to classify the UIP and NSIP, and features were selected through sequential-forward floating feature selection. For the evaluation, 54 HRCT images of UIP (n=26) and NSIP (n=28) patients clinically diagnosed by a pulmonologist were included and evaluated. The classification accuracy was measured based on a fivefold cross-validation with 20 repetitions using random shuffling. For comparison, thoracic radiologists assessed each case using HRCT images without clinical information or diagnosis. The accuracies of the radiologists' decisions were 75 and 87%. The accuracies of the CADD system using different features ranged from 70 to 81%. Finally, the accuracy of the proposed CADD system after sequential-forward feature selection was 91%.

FDG-PET/CT in the prediction of pulmonary function improvement in nonspecific interstitial pneumonia. A Pilot Study

PurposeOur study aimed to analyse the characteristics of nonspecific interstitial pneumonia (NSIP) using FDG-PET/CT (PET) and to evaluate its ability to predict the therapeutic response. ProceduresEighteen NSIP patients were included. Maximum standardized uptake value (SUVmax), FDG uptake extent (in percentage of lung volume), high resolution CT scan (HRCT) elementary lesions, and HRCT fibrosis score were recorded. The predictive value of the parameters for lung function improvement was evaluated using logistic regression and Receiver Operating Characteristic (ROC) curve analysis (n=13/18). ResultsAll patients had an increased pulmonary FDG uptake (median SUVmax=3.1 [2–7.6]), with a median extent of 19% [6–67]. Consolidations, ground-glass opacities, honeycombing and reticulations showed uptake in 90%, 89%, 85% and 76%, respectively. FDG uptake extent was associated with improvement of pulmonary function under treatment (increase in forced vital capacity>10%, p=0.03), whereas SUVmax and HRCT fibrosis score were not (p>0.5). For FDG uptake extent, ROC analysis showed an area under the curve at 0.85±0.11 and sensitivity/specificity was 88%/80% for a threshold fixed at 21%. ConclusionsIncreased FDG uptake was observed in all NSIP patients, both in inflammatory and fibrotic HRCT lesions. The quantification of FDG uptake extent might be useful to predict functional improvement under treatment.

Nonspecific interstitial pneumonia: time to be more specific?

There is growing speculation that idiopathic nonspecific interstitial pneumonia (NSIP) is, in reality, a grouping of separate disorders with a common histologic pattern. In this review, distinct clinical, imaging, and serologic features providing support for this premise are detailed and discussed. The diagnosis of idiopathic NSIP is often uncertain because of its clinical and imaging diversity. In a landmark study of inter-multidisciplinary group diagnostic variation, there were striking discrepancies between seven expert groups (κ = 0.24) in diagnoses of idiopathic NSIP. Recent histologic observations provide support for the concept of an NSIP/organizing pneumonia overlap, distinct from isolated NSIP. An important group of NSIP patients with features of 'undifferentiated connective disease', historically classified as an idiopathic NSIP subgroup, have been shown to have a lower mortality than idiopathic NSIP patients without features of autoimmune disease. The recently proposed entity of 'interstitial pneumonia with autoimmune features' includes many patients with a histologic or imaging pattern of NSIP, shown by Oldham and colleagues to have a similar survival to patients with connective tissue disease-related NSIP. The concept of idiopathic NSIP as a grouping of separate disorders with a common histologic pattern provides a template for potentially important pathogenetic insights.

Nonspecific Interstitial Pneumonia: What Is the Optimal Approach to Management?

We reviewed current aspects of the clinical and pathogenic profile of nonspecific interstitial pneumonia (NSIP), to better elucidate the complex issue of management and treatment options for NSIP patients. Recent findings suggest that idiopathic NSIP is a complex clinical entity with a disease spectrum that includes at least three different phenotypes: NSIP associated with autoimmune features, emphysema, and familial interstitial lung disease. This distinction, based mainly on clinical findings, may be of critical importance when it comes to making a decision on patients' management. This hypothesis warrants further studies. Currently, two major radiologic-pathologic different profiles have been well established. First, the "inflammatory type" characterized by prominent lymphocytic inflammation both on biopsy and bronchoalveolar lavage (BAL), and high-resolution computed tomography (HRCT) with mixed NSIP/organizing pneumonia pattern that tends to have a better response to corticosteroid and immunosuppressive treatment. Second, the "highly fibrotic" subgroup that shows prominent reticular changes and traction bronchiectasis by HRCT, high fibrotic background on biopsy, and no lymphocytosis on BAL. The latter fibrotic NSIP is the subgroup with less potential to respond to immunosuppressive treatment and a marginal risk to evolve into "full-blown idiopathic pulmonary fibrosis." The management of patients with fibrotic, progressive, and immunosuppressive treatment, refractory NSIP remains uncertain, and further studies are needed to address the role of antifibrotic drug in this settings. Oxygen therapy, pulmonary rehabilitation, and lung transplantation are of importance in the current management of severe, progressive, and refractory NSIP patients.

Lung diffusing capacity for nitric oxide as a marker of fibrotic changes in idiopathic interstitial pneumonias.

Lung diffusing capacity for carbon monoxide (DLCO) is decreased in both usual interstitial pneumonia-idiopathic pulmonary fibrosis (UIP-IPF) and nonspecific interstitial pneumonia (NSIP), but is moderately related to computed tomography (CT)-determined fibrotic changes. This may be due to the relative insensitivity of DLCO to changes in alveolar membrane diffusive conductance (DMCO). The purpose of this study was to determine whether measurement of lung diffusing capacity for nitric oxide (DLNO) better reflects fibrotic changes than DLCO DLNO-DLCO were measured simultaneously in 30 patients with UIP-IPF and 30 with NSIP. Eighty-one matched healthy subjects served as a control group. The amount of pulmonary fibrosis was estimated by CT volumetric analysis of visually bounded areas showing reticular opacities and honeycombing. DMCO and pulmonary capillary volume (VC) were calculated. DLNO was below the lower limit of normal in all patients irrespective of extent and nature of disease, whereas DLCO was within the normal range in a nonnegligible number of patients. Both DLNO and DLCO were significantly correlated with visual assessment of fibrosis but DLNO more closely than DLCO DMCO was also below the lower limit of normal in all UIP-IPF and NSIP patients and significantly correlated with fibrosis extent in both diseases, whereas VC was weakly correlated with fibrosis in UIP-IPF and uncorrelated in NSIP, with normal values in half of patients. In conclusion, measurement of DLNO may provide a more sensitive evaluation of fibrotic changes than DLCO in either UIP-IPF or NSIP, because it better reflects DMCO.

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.

Nonspecific interstitial pneumonia: survival is influenced by the underlying cause.

Idiopathic, nonspecific interstitial pneumonia (NSIP) is most often associated with various clinical disorders, including connective tissue diseases (CTDs) and chronic hypersensitivity pneumonitis (cHP). Emerging evidence also suggests that "idiopathic" NSIP may be the lung manifestation of undifferentiated CTD (UCTD). However, whether or not NSIP outcome is influenced by the underlying cause remains uncertain. This retrospective study included 127 biopsy-proven NSIP patients (65 women, mean ± sd age 55 ± 12 years). Survivals were estimated using a Kaplan-Meier curve and compared using the log-rank test. Multivariate analyses were based on a Cox model. 15 (11.8%) patients had cHP, 29 (22.8%) had CTD, 32 (25.2%) satisfied the Kinder criteria for UCTD and 51 (40.1%) had idiopathic NSIP. At the end of follow-up (mean ± sd 64 ± 54 months), a difference in survival was observed between aetiological groups (p=0.002). Survival was better for UCTD than for idiopathic NSIP (p=0.020) and similar to that observed for CTD. cHP survival tended to be poorer than that of idiopathic NSIP (p=0.087) and was an independent predictor of mortality (hazard ratio 2.17, 95% CI 1.05-4.47; p=0.035). NSIP outcome is influenced by its cause. cHP exhibits the highest mortality. UCTD does not differ from CTD supporting the concept of autoimmune NSIP, with a prognosis that is better than that of idiopathic NSIP.

P9 Cough Is Prevalent In Higher Proportion Of Older Patients With Both Idiopathic Pulmonary Fibrosis And Non-specific Interstitial Lung Disease

Introduction Cough is a major symptom of Idiopathic Pulmonary fibrosis (IPF), a progressive, fatal lung disease with median survival of 3 years. The first study to suggest cough as an independent predictor of disease progression, reported it in 84% of the population. 1 The only study to quantify cough in 19 IPF patients, reported strong correlation between objective cough counts and cough related quality of life 2 There is a lack of studies investigating the prevalence, pathogenesis or treatment of cough in IPF. We set up a study to evaluate the prevalence of cough in an incident IPF and Non specific Interstitial Pneumonia (NSIP) population. Methods A prospective, multi-centre, observational, cohort study, PROFILE-Central England (September 2009 to June 2014) was set up. Patients had a diagnosis of definite or probable IPF or NSIP based on the ATS consensus. Leicester cough questionnaire (LCQ) was used to assess presence or absence of cough at baseline. Furthermore,the cohort was divided into 3 groups to assess severity of cough: Mild (17–20), Moderate (11–16.9) and Severe ( Results 312 incident patients with IPF or NSIP were enrolled. 261/312(83.6%) patients had incident IPF whilst 51/312(16.4%) had NSIP. The mean age of the cohort was 73.5 years (35–90 years). 235/312(76%) were males with mean age 73.7 years (47–90 years); 74/312(24%) were females with mean age of 72.9 years (35.8–88.8 years). 261/312(83.6%) reported cough compared with 51/312(16.4%) who reported no cough. Of the patients who reported cough, 45/261(17.2%) had severe cough, 112/261(42.9%) had moderate cough and 104/261(39.8%) had mild cough. There was no effect of gender, however, older cohort reported more cough (age >55 years; p = 0.014). Smoking may be a confounder, however the number of current smokers in the cohort is too small (p = 0.05). Interestingly both NSIP and IPF cohort reported cough; however, proportionally NSIP patients have less cough (14/51,27.4%) compared with IPF (37/261, 14%). Conclusions Cough occurs in a huge majority of patients with both IPF and NSIP. Cough appears to be a greater problem in older patients. References Ryerson CJ et al . Cough predicts prognosis in idiopathic pulmonary fibrosis. Respirology . 2011 Aug;16(6):969–75 Key AL et al . Objective cough frequency in Idiopathic Pulmonary Fibrosis. Cough . 2010;6:4

Nonspecific interstitial pneumonia and usual interstitial pneumonia: comparison of the clinicopathologic features and prognosis.

Nonspecific interstitial pneumonia (NSIP) has recently been proposed as a histologic type of idiopathic interstitial pneumonia (IIP), but its broad spectrum of clinicopathologic findings and variable prognosis are poorly understood. It is particularly unclear how NSIP and usual interstitial pneumonia (UIP) are related. The present study investigated the clinicopathologic features and prognosis of NSIP, and its differential diagnosis from UIP. The clinicopathologic findings and prognosis in 21 NSIP and 18 UIP patients who underwent surgical or video-assisted thoracoscopic lung biopsy were reviewed. NSIP was more frequent in women and showed nonspecific clinical manifestations. High-resolution computed tomography (HRCT) demonstrated ground-glass, net-like, and patchy attenuation in both lungs. Semiquantitative HRCT showed a median fibrosis score of 3 (range, 0 to 7) in NSIP patients and 5 (range, 2 to 7) in UIP patients (P<0.01). On histopathologic examination, NSIP cases were heterogeneous and the findings could be categorized into cellular and fibrosing patterns. The mean age of the NSIP and UIP patients was 48 and 60 years, respectively. The frequencies of fibroblast foci, myogelosis, honeycomb lesions, and pulmonary structural destruction in NSIP and UIP patients were 16.7% and 100% (P<0.001), 22.2% and 85.7% (P<0.05), 16.7% and 92.9% (P<0.001), and 27.8% and 100% (P<0.05), respectively. The responses to glucocorticoid treatment and the prognosis were significantly greater in NSIP than those in UIP. NSIP was difficult to be differentiated from UIP by general clinical manifestations, but HRCT can be helpful for this purpose. Definitive diagnosis depends on the results of surgical lung biopsy.

Serum heat shock protein 47 levels are elevated in acute interstitial pneumonia

BackgroundHeat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. We hypothesized that HSP47 could be a useful marker for fibrotic lung disease. The aim of this study was to evaluate serum levels of HSP47 in patients with various idiopathic interstitial pneumonias (IIPs).MethodsSubjects comprised 9 patients with acute interstitial pneumonia (AIP), 12 with cryptogenic organizing pneumonia (COP), 16 with nonspecific interstitial pneumonia (NSIP), 19 with idiopathic pulmonary fibrosis (IPF), and 19 healthy adult volunteers.ResultsPatients with AIP had serum HSP47 levels that were significantly higher than those of COP, NSIP or IPF patients and those of healthy volunteers. In contrast, serum levels of HSP47 among patients with COP, NSIP, IPF, and healthy volunteers did not differ significantly. Receiver operating characteristic curves revealed that the cut-off level for HSP47 that resulted in the highest diagnostic accuracy for discriminating between AIP and COP, NSIP, IPF, and healthy controls was 859.3 pg/mL. The sensitivity, specificity, and diagnostic accuracy were 100.0%, 98.5%, and 98.7%, respectively.ConclusionThe present results demonstrate that, among patients with various IIPs, serum levels of HSP47 were elevated specifically in patients with AIP.

Sleep Apnea Management in “Possible IPF” and “Idiopathic NSIP”: A Case- Series

Purpose: The clinical course of patients with possible idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia (NSIP) is not well understood. While these patients are clinically followed for disease progression before rendering therapy, the import of sleep-disordered breathing on the disease course is unknown. Methods: Retrospective analysis of possible IPF and idiopathic NSIP patients seen at a single center with review of clinical data pertinent to therapy for co-morbid sleep-disordered breathing was done. Results: 7 patients with possible IPF based upon radiologic possible UIP patterns (5 male and 2 female) and 6 patients with idiopathic NSIP (5 female and 1 male) were followed for an average duration of 40 and 30 months respectively. 6/7 patients with possible IPF required continuous positive airway pressure (CPAP) therapy for sleepdisordered breathing and out of this 5/6 were compliant with therapy. Of idiopathic NSIP patients, 2/6 presented with acute exacerbations. All 6 patients required therapy for OSA out of which 5/6 were treated with CPAP and 1 treated with supplemental oxygen. Patients with possible IPF appeared to stabilize their disease following treatment of OSA and none of the study patients experienced any recurrence of acute exacerbations on CPAP therapy. Conclusions: OSA can be an important problem in patients with possible IPF and idiopathic NSIP. Treatment with nocturnal CPAP therapy in these patients with concomitant OSA may result in stability of underlying interstitial lung disease.