Usual Interstitial Pneumonia Group Research Articles

Differential Diagnosis of Fibrotic Hypersensitivity Pneumonitis with Its Non-Fibrotic Phenotype and Usual Interstitial Pneumonia During High-Resolution Computed Tomography

Background. Diagnosis of hypersensitivity pneumonitis (HP) using high-resolution computed tomography (HRCT) is not an easy task. The most difficult aspects of the disease include differential diagnosis of its fibrotic (fHP) and non-fibrotic (nfHP) phenotypes, as well as their differentiation from usual interstitial pneumonia (UIP) in idiopathic pulmonary fibrosis. The determination of fibrous changes at an early stage of development can significantly accelerate the beginning of antifibrotic therapy and improve the prognosis.Objective: to identify key HRCT signs for reliable differentiation of fHP and nfHP, to carry out differential diagnostics between fHP and UIP.Material and methods. The data of 73 patients with morphologically verified HP, in whom HRCT had been performed, were retrospectively analysed. In 21 patients, nfHP was determined, and in 52 patients fHP was identified. The comparison group consisted of 24 patients with a typical radiological UIP pattern. The analysis of the changes detected during HRCT was carried out by qualitative and semi-quantitative methods. The significance of qualitative differences in a sign manifestation was assessed by Fisher’s exact test, semi-quantitative differences were evaluated using Mann–Whitney test.Results. The results of the study allow to assume, that the presence and degree of manifestation of certain HRCT signs significantly differ between the selected groups of patients in qualitative and/or semi-quantitative terms. In cases of НP, the distribution of changes was mostly uniform and diffuse, with no clear predominance in certain lobes. In UIP, diffuse craniocaudal distribution took place, and in the axial plane, the changes were mainly subpleural in nature.Conclusion. Based on the results of the study, it can be assumed that fHP significantly differs from nfHP in such features as the presence and degree of manifestation of ground glass and honeycombing symptoms, reticular changes and traction bronchiectases. When comparing the fHP and UIP groups, the distinctive signs of fHP were centrilobular nodules, mosaic pattern, as well as diffuse axial sign distribution.

Impact of HRCT pattern on six-minute walk test in patients with interstitial lung disease-An observational study.

Forced vital capacity (FVC) and six-minute walk distance (6MWD) are robust markers in interstitial lung diseases (ILD) to assess severity and prognosis. It is unknown whether high-resolution computed tomography pattern has any independent effect on the exercise capacity in ILD. We compared six-minute walk test (6MWT) parameters between usual interstitial pneumonia (UIP) and non-UIP ILD after adjusting for FVC. Data from a tertiary care ILD clinic were retrospectively analysed. Based on HRCT, patients were classified as UIP and non-UIP. 6MWT parameters and FVC were recorded for enrolled patients. 6MWD, distance-saturation product (DSP) and exertional desaturation were compared between UIP and non-UIP, using analysis of covariance (ANCOVA), with per cent predicted FVC as covariate. Patients were grouped as mild (≥70%), moderate (51%-69%) and severe (≤50%) based on FVC severity. Out of 169 patients enrolled, only patients with all three data points: spirometry, 6MWT and HRCT were included in the analysis (n = 139). UIP group comprised 56 (40.3%), while non-UIP group had 83 (59.7%) patients. More females and lesser smokers were present in non-UIP group. Mean predicted FVC% was similar between the two HRCT groups (P = 0.611) and had a statistically significant, though very weak to weak correlation with 6MWT parameters {6MWD (r = 0.138); pred 6MWD% (r = 0.170); desaturation (r = -0.227); DSP index (r = 0.166)}. Analysis of covariance showed no statistically significant difference in the 6MWT parameters between UIP and non-UIP groups for similar FVC levels. For a similar level of lung function, exercise capacity was similar for patients with UIP and non-UIP pattern ILD.

POSITIVE ENVISIA GENOMIC CLASSIFIER RESULT PREDICTS CLINICAL PROGRESSION IN FIBROTIC INTERSTITIAL LUNG DISEASE

POSITIVE ENVISIA GENOMIC CLASSIFIER RESULT PREDICTS CLINICAL PROGRESSION IN FIBROTIC INTERSTITIAL LUNG DISEASE

Chest ultrasound findings in usual interstitial pneumonia patterns: a pilot study

It is unknown what role chest ultrasound plays in distinguishing the various usual interstitial pneumonia (UIP) patterns of high-resolution chest tomography (HRCT). The purpose of this study was to see if there was a link between the results of chest ultrasound (u/s) and HRCT in patients with idiopathic pulmonary fibrosis (IPF). We performed chest u/s in 16 patients with UIP and probable UIP patterns to indeterminate UIP and alternative diagnosis patterns in this single center prospective study to determine any possible relationship with the HRCT findings. A chest radiologist reviewed each HRCT to determine the pattern in accordance with the American Thoracic Society (ATS) / European Respiratory Society (ERS) Guidelines. The local multidisciplinary committee validated the patients' diagnoses before they were included. When compared to the indeterminate for UIP or alternative diagnosis pattern group, there was a trend (p=0.07) toward the presence of more B lines in UIP or probable UIP patterns. There was no statistically significant difference in the presence of small, large, white lung, or pleural line thickening >5mm. Subgroup analysis revealed that patients with honeycombing were more likely to have a fragmented pleural line (p=0.04). To summarize, in our pilot study, chest u/s appears unable to differentiate UIP and probable UIP patterns from indeterminate UIP and alternative diagnosis patterns. However, it appears that this technique can be used to recognize the honeycombing pattern.

Patterns of lung diseases predict survival in patients with MPO-ANCA-associated vasculitis: a single-center retrospective study.

This study aimed to explore differences in clinical features and prognosis among patients with varied myeloperoxidase (MPO) antineutrophil cytoplasmic antibody-associated vasculitis (MPO-AAV) associated lung diseases. Patients with MPO-AAV-associated lung diseases were enrolled in this retrospective cohort study at a single center. Clinical features and laboratory data at the time of diagnosis were compared among patients with various lung disease patterns. Kaplan-Meier and Cox regression analyses were performed to analyze overall survival. A total of 155 patients were finally included and categorized into five groups, as follows: 72 had a usual interstitial pneumonia (UIP) pattern, 40 had non-UIP interstitial pneumonia, 18 had bronchiectasis (BR), 13 had necrotizing granuloma (NG), and 12 had diffuse alveolar hemorrhage (DAH). Among the five groups, patients with DAH had higher dyspnea and hemoptysis frequencies, lower PaO2/FiO2 levels, elevated C-reactive protein levels, and the poorest prognosis. The overall survival (OS) in the DAH group (median OS: 3.2months) was significantly poorer than that in the NG group (median OS: not reached, log rank P < 0.001), the BR group (median OS: not reached, log rank P < 0.001), and the non-UIP IP group (median OS: 61.1months, log rank P = 0.001). The UIP group had significantly more ex-smokers than the other groups (P < 0.001) and the second poorest survival (median OS: 39.1months). The NG group tended to have female predominance, a higher incidence of ENT involvement, less severe renal involvement, and the best survival. After adjusting for multi-model Cox regression analysis, DAH and UIP (hazard ratio: 19.301 and 9.940, respectively, compared with NG) were independent predictors of all-cause mortality. Various patterns of lung disease-associated MPO-AAV may potentially predict patient survival. Key Point • The present study described the clinical and prognostic features of various lung diseases-associated MPO-AAV, indicating the potential prediction for the survival of MPO-AAV patients.

Safety and Diagnostic Yield of Radial Probe Endobronchial Ultrasound-Guided Biopsy for Peripheral Lung Lesions in Patients with Idiopathic Pulmonary Fibrosis: A Multicenter Cross-Sectional Study

Background: Radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB) is widely used for diagnosis of peripheral lung lesions (PLLs). To date, there have been no reports regarding the clinical outcomes of RP-EBUS-TBLB for PLLs in patients with idiopathic pulmonary fibrosis (IPF). Objectives: This study was performed between October 2017 and December 2019 to identify the safety and diagnostic performance of RP-EBUS-TBLB in IPF patients. Methods: Patients were divided into the usual interstitial pneumonia (UIP) group (n = 39, 4%), the probable UIP group (n = 12, 1%), and the noninterstitial lung disease (non-ILD) group (n = 903, 95%). Results: The diagnostic yield was significantly lower in the UIP group than in the non-ILD group (62% vs. 76%; p = 0.042), but there were no significant differences between the UIP and probable UIP groups (62% vs. 83%; p = 0.293) or the probable UIP and non-ILD groups (83% vs. 76%; p = 0.741). Multivariate logistic analysis showed that the mean diameter of PLLs, positive bronchus sign on CT, and “within the lesion” status on EBUS were independently associated with success of the procedure. Especially, the presence of the UIP pattern on CT (OR, 0.385; 95% CI: 0.172–0.863; p = 0.020) was independently associated with failed diagnosis. Among patients with UIP, “within the lesion” status on EBUS (OR, 25.432; 95% CI: 2.321–278.666; p = 0.008) was shown to be a factor contributing to a successful diagnosis. Overall, there were no significant differences in complication rates among the 3 study groups. Conclusion: RP-EBUS-TBLB can be performed safely with an acceptable diagnostic yield, even in patients with IPF.

Non-invasive IGFBP1, IGFBP2 biomarkers as predictors and outcomes of usual interstitial pneumonia (UIP) therapeutic response

BackgroundUsual interstitial pneumonia (UIP) is a fatal disease that is associated with poor prognosis and survival. Several growth factors such as IGFs (insulin-like growth factors) and IGFBPs (insulin-like growth factor binding proteins) seem to take part to this pathogenesis.Pirfenidone is an immunosuppressant drug that is thought to have anti-inflammatory and anti-fibrotic effects both in vitro and in vivo.ObjectiveTo assess IGFBP1 and IGFBP2 as non-invasive biomarkers for prediction and outcomes of UIP clinical activity and therapeutic response to the anti-fibrotic pirfenidone.ResultsSerum levels of IGFBP1 and IGFBP2 were significantly higher in the UIP group than in the healthy subjects (p ≤ 0.005). After 6 months therapy, UIP patients were divided into 2 groups according to improvement in MRC dyspnea grading into clinically improved and non-improved groups. 6MWT and SPaO2 were significantly improved in the clinically improved group compared to the non-improved one with no differences as regards other parameters (p < 0.0001). Both IGFBP1 and IGFBP2 were significantly decreased in serum while only IGFBP2 was decreased in BAL of all UIP after completing 12 months therapy.ConclusionIGFBP1 and IGFBP2 were increased in active UIP patients and reduced after 12 months anti-fibrosing therapy. IGFBPs may be promising biomarkers and predictors of response to therapy in UIP.

Treatment with antifibrotic agents in idiopathic pleuroparenchymal fibroelastosis with usual interstitial pneumonia.

BackgroundThere are no established therapeutic options available for idiopathic pleuroparenchymal fibroelastosis (IPPFE) apart from supportive care and lung transplantation. Furthermore, it is known that IPPFE with a usual interstitial pneumonia (UIP) pattern and lower lobe predominance is a disease entity distinct from idiopathic pulmonary fibrosis (IPF). To our knowledge, few studies are available that report on the efficacy of antifibrotic agents for IPPFE with UIP.AimThe aim of this study was to compare the efficacy of antifibrotic agents between IPPFE with UIP and typical IPF in real-world clinical practice.Patients and methodsA retrospective analysis was performed on the medical records of all patients at two interstitial lung disease centres. Sixty-four patients were diagnosed as having IPPFE with UIP and 195 patients were diagnosed with typical IPF. We compared the efficacy of antifibrotic agents between these two groups.ResultsSurvival time was significantly shorter in the patients with IPPFE with UIP. Some 125 patients were administered antifibrotic agents for over 6 months (34 with IPPFE with UIP and 91 with typical IPF). Reduced forced vital capacity (FVC) 6 months after treatment with antifibrotic agents was significantly greater in the IPPFE with UIP group than in those in the typical IPF group. Moreover, the change in % predicted FVC was significantly greater during the follow-up in patients with IPPFE with UIP compared with those with typical IPF.ConclusionsThe efficacy of antifibrotic agents was limited in patients with IPPFE with UIP. Thus, IPPFE with UIP remains a fatal and progressive disease.

Computed tomography patterns predict clinical course of idiopathic pulmonary fibrosis

BackgroundA new clinical guideline for idiopathic pulmonary fibrosis (IPF) uses high-resolution computed tomography (HRCT) patterns for diagnostic purposes. However, it is unknown how they relate to the IPF clinical course. We aimed to investigate whether HRCT patterns could be used to predict lung function changes and survival in patients with IPF.MethodsClinical data were retrospectively reviewed in 337 patients with IPF (all biopsy-proven cases). HRCT patterns were classified according to the 2018 IPF diagnostic criteria.ResultsThe median follow-up was 46.9 months. The mean age was 62.5 years, and 74.2% were men. Among the HRCT patterns, usual interstitial pneumonia (UIP), probable UIP, indeterminate for UIP, and an alternative diagnosis were identified in 163 (48.4%), 110 (32.6%), 33 (9.8%), and 31 (9.2%) patients, respectively. The indeterminate for UIP group showed higher lung function and exercise capacity and better prognosis than the other groups. They also had a lesser decline in lung function than the other groups during follow-up. In the multivariate Cox analysis, which was adjusted by age, smoking status, lung function, exercise capacity, and use of antifibrotic agents, indeterminate for UIP pattern was found to be an independent prognostic factor (hazard ratio 0.559, 95% confidence interval 0.335–0.933, P = 0.026). However, the probable UIP group had similar lung function changes and prognosis when compared the UIP group.ConclusionsOur results suggest that indeterminate for UIP pattern on HRCT may predict a more favorable clinical course in patients with IPF, supporting the validity of the new IPF diagnostic guidelines.

Chest High-resolution Computed Tomography Imaging Features of Lung Involvement in Rheumatoid Arthritis

Objective To explore the chest high-resolution computed tomography (HRCT) features in patients with rheumatoid arthritis (RA) complicated with pulmonary involvement. Methods Totally 161 patients with RA with lung involvement were collected from June 2014 to May 2018. The chest HRCT findings were retrospectively analyzed. According to the imaging features as well as the results of history taking,pulmonary function test,pathology,and bronchoalveolar lavage fluid test,RA-related lung diseases (RA-LD) were classified and their clinical characteristics were compared. Results These 161 RA-LD patients (56 males and 105 females) whose mean age at diagnosis was (60.7±12.8) years (14-85 years) included 87 cases of usual interstitial pneumonia (UIP) (including 16 cases of possible UIP),44 cases of non-specific interstitial pneumonia (NSIP),10 cases of organizing pneumonia,7 cases of lymphocytic interstitial pneumonia,9 cases of small airway disease (SAD) (including 8 cases of bronchiolitis obliterans and 1 case of follicular bronchiolitis),and 4 other lung manifestations (including 3 cases of diffuse alveolar hemorrhage and 1 case of rheumatoid nodules). The UIP group had the oldest average age [(63.3±12.1) years old] and the highest smoking rate (41.4%). The SAD group had the youngest average age [(54.7±15.1) years old] and there was no smoking history. There were significant differences between these two groups (P=0.020,P<0.001). Seventy patients (43.5%) with RA-LD were complicated with pleural lesions. Conclusions RA involving the lung is common and has varied imaging manifestations,with interstitial lung diseases (mainly UIP and NSIP) being the most important manifestations. RA patients should undergo lung HRCT as early as possible to identify the lung involvement and related types.

Evaluation of Cyclin D1 as a Discriminatory Immunohistochemical Biomarker for Idiopathic Pulmonary Fibrosis.

Distinction of idiopathic pulmonary fibrosis (IPF) from other chronic fibrosing interstitial pneumonitides, such as hypersensitivity pneumonitis (HP) and connective tissue diseases, is critical due to varied biological and clinical outcomes. However, their histologic overlaps often pose diagnostic challenges. A recent study suggested an association of herpesvirus saimiri infection with IPF. Productive viral infection is associated with coexpression of pirated mammalian protein cyclin D1, shown to be overexpressed by immunohistochemistry (IHC) in the regenerating alveolar epithelium in IPF but not in normal lungs. We evaluated the diagnostic utility of cyclin D1 to discriminate between IPF and other fibrosing interstitial lung diseases. A retrospective study of cyclin D1 IHC expression in 27 consecutive cases of chronic fibrosing interstitial lung diseases from 2011 to 2017: 12 usual interstitial pneumonia (UIP) pattern; 5 nonspecific interstitial pneumonia pattern; 3 HP pattern; 7 unclassifiable was performed. Five cases of normal lung obtained from lobectomy specimen for malignancy are included as control. Immunoreactivity was graded semiquantitatively on a scale of 0 to 3. Cyclin D1 staining was uniformly strongly positive in all cases evaluated in the study, particularly in proliferating type II pneumocytes in the region of fibrosing areas. There was no statistical difference in the extent of cyclin D1 expression between UIP and non-UIP groups (2.7 vs. 2.5) and IPF versus non-IPF groups (2.7 vs. 2.4). Cyclin D1 expression is lower in control group compared with UIP groups (1.2 vs. 2.7). Cyclin D1 is not a specific marker of UIP pattern/IPF. The high expression of cyclin D1 in lung tissue of fibrosing interstitial pneumonitides regardless of etiology most likely correlates with proliferation in type II pneumocytes.

Radiological patterns of pulmonary involvement may predict treatment response in rheumatoid arthritis: A retrospective study.

There have been no reports on the relationship between lung radiological patterns and rheumatoid arthritis (RA) disease activity or RA treatment response in patients with RA-associated lung disease (RA-LD). Patients with RA-LD who underwent treatment for RA from April 2005 to March 2015 were retrospectively evaluated. RA-LD patients were divided into three groups based on high-resolution computed tomography (HRCT) patterns [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and bronchiolitis]. The disease activity score of 28 joints-erythrocyte sedimentation rate (DAS28-ESR) and the response of RA to treatment, as measured by the European League Against Rheumatism (EULAR) response criteria, were investigated. A total of 77 patients (21 with UIP, 23 with NSIP, and 33 with bronchiolitis) were enrolled. Median scores (interquartile range) on the DAS28-ESR at baseline were 5.27 (4.76-5.74), 5.48 (4.24-6.34), and 5.04 (3.90-5.66) for UIP, NSIP, and bronchiolitis, respectively; there were no statistical differences between the three groups (p = 0.412). One year after baseline, 19 (90%), 14 (61%), and 19 (58%) of patients in the UIP, NSIP, and bronchiolitis groups, respectively, were considered good or moderate responders, as evaluated using the EULAR response criteria; there was a significant difference between these three groups (p = 0.014). Multiple logistic regression analysis revealed that the UIP pattern was significantly associated with good or moderate response to RA treatment 1 year after baseline (p = 0.012). These results suggest that NSIP and bronchiolitis HRCT patterns may be risk factors for resistance to RA therapy.

A clinicopathological study of surgically resected lung cancer in patients with usual interstitial pneumonia

BackgroundThe clinicopathological characteristics of lung cancer with concomitant usual interstitial pneumonia (UIP) are insufficiently understood. This study aimed to elucidate a characteristic pathological feature of lung cancer that develops in patients with UIP, with a focus on the location of its onset. MethodsWe reviewed surgically obtained specimens, including 547 tumors from 526 patients who underwent lobectomy for lung cancer. Surveyed patients were classified into three groups: patients with UIP (UIP group), patients with lung pathology other than UIP (non-UIP group), and patients without any associated lung pathology (normal group). The histology as well as the lobe and location of the onset of lung cancer were compared among these groups. The peripheral location was subdivided into subpleural, inner and tumor involved centrally secondary to extension. ResultsThe UIP group comprised 82 patients (male, 71 [87%]; mean age, 71 years; smoking rate, 94%), the non-UIP group comprised 334 patients (male, 267 [80%]; mean age, 69 years; smoking rate, 81%), and the normal group comprised 110 patients (male, 33 [30%]; mean age, 63; smoking rate, 29%). No statistical differences were noted in sex, mean age, or smoking index between the UIP and non-UIP groups. Compared with the non-UIP group, the frequency of squamous cell carcinoma (63% vs. 32%), lower lobe origin (76% vs. 32%), and subpleural location (24% vs. 5%) were significantly higher in the UIP group. ConclusionsLung cancers in patients with UIP show a predilection for the subpleural region, where UIP is also thought to originate.

Non-specific and Usual Interstitial Pneumonia, Short-Term Survival After Surgical Biopsy

To the Editors, Idiopathic interstitial pneumonia (IIP) is a diagnostic challenge. The diagnostic work-up in general includes medical history, physical examination, lung function tests, chest X-ray, high-resolution computed tomography and bronchoalveolar lavage. If no clinical diagnosis can be established on the basis of these data, a surgical lung biopsy might be indicated. In this setting, possible therapeutic and prognostic implications should be weighed against the risk of postoperative complications such as infections, prolonged air leakage, respiratory failure, acute exacerbation of underlying disease and even mortality. Review of literature shows that postoperative mortality after surgical lung biopsy in IIP was found to be 4.8 % after 30 days and 6 % after 90 days [1]. Reported risk factors for mortality were low diffusing capacity for carbon monoxide (DLCO) and low forced vital capacity (FVC) [2, 3]. There are reports suggesting that surgical lung biopsy itself increases the risk of acute exacerbation of underlying disease [2, 3]. The aim of this study was to evaluate the 30- and 90-day mortality rate after surgical lung biopsy in two histological distinct groups of patients: one with a histological pattern of usual interstitial pneumonia (UIP) and one with a pattern of non-specific pneumonia (NSIP). In this retrospective study, we included all patients with a histological UIP or NSIP who underwent surgical lung biopsy between 1993 and 2011 in our centre. Baseline characteristics are presented in Table 1. Data on mortality rate at 30 and 90 days, length of postoperative hospital stay, duration of air leakage, time to drain removal after surgery and infectious complications were collected. Table 1 Baseline characteristics Data of 69 patients were analysed (Table 1). There were 23 patients with histological NSIP and 46 with UIP. Baseline characteristics showed significant differences between both groups: mean forced expiratory volume in 1 s (FEV1) and diffusion capacity (DLCO) were lower in the NSIP group compared with the UIP group. Patients with a UIP pattern in this study were more often male and were older. No significant differences were found in FVC, total lung capacity, Body Mass Index (BMI) and smoking status. Overall, the 90-day mortality rate after surgical lung biopsy in all patients was 11.6 % (8 out of 69). In the UIP group, all patients who died underwent an open lung biopsy, the 30-day mortality rate was 8.7 % (4 out of 46) and the 90-day mortality rate was 15.2 % (7 out of 46). The median pre-operative FVC was 86 % and DLCO 46 % of the seven patients who passed away. Two patients died of pneumonia with radiologic evidence of progression of fibrosis. Post-mortem examination revealed diffuse alveolar damage in one case. Three patients died in the second and third month due to progression of fibrosis, and in two cases, this was proven by post-mortem examination and in one case radiologically. One cause of death was unknown due to loss to follow-up. Among seven patients with UIP who died, five were ultimately diagnosed to have idiopathic pulmonary fibrosis (IPF) and two to nonclassifiable interstitial pneumonia. In the NSIP group, only one patient died due to pneumonia in the first month after surgery. The 30- and 90-day mortality rates were both 4.3 % in the NSIP group. No significant differences were found in postoperative hospital stay (p = 0.906), duration of air leakage (p = 0.721), time to drain removal after surgery (p = 0.65) and infectious complications (p = 0.977) between the NSIP and UIP group. There was no correlation between year of surgery and mortality. Although the difference in mortality rate between the UIP and NSIP group was not statistically significant, we observed a trend towards a higher mortality rate in patients with UIP pattern, which is in agreement with reports in the literature [2, 3]. Interestingly, all deceased UIP patients with a known cause of death showed progression of fibrosis, while no progression of fibrosis was observed in the patient who died in the NSIP group. This observation suggests that the UIP non-survivors, who had relatively good pre-operative lung functions compared to the all NSIP patients, experienced rapid progression of their disease which cannot be excluded to be related to the surgical procedure. We hypothesize that this rapid progression of fibrosis might be induced by the surgical procedure itself causing increased damage of the highly vulnerable alveolar epithelium. Increased vulnerability of the alveolar wall appears to be a fundamental problem in IPF. In conclusion, mortality after surgical lung biopsy is relatively high, especially in patients with a histological pattern of UIP. We think that these results should be taken into account when considering open lung biopsy in patients with suspected IIP.

Clinical findings and outcomes in patients with possible usual interstitial pneumonia

Patients with possible usual interstitial pneumonia (UIP) constitute a substantial group, and their clinical characteristics and outcomes are not well defined. We compared the clinical characteristics and survival between patients with possible UIP and the UIP pattern. We evaluated 62 patients with possible UIP and 544 patients with the UIP pattern. Both groups were diagnosed by clinical characteristics and high-resolution computed tomography (HRCT) findings. Two radiologists performed radiological evaluation based on the new idiopathic pulmonary fibrosis (IPF) guidelines. Two risk-stratification methods were used to compare UIP pattern and possible UIP patients. The groups had similar demographic and clinical characteristics. Pulmonary function tests revealed no significant differences in lung volumes between the 2 groups. However, DLCO was significantly lower with the UIP pattern than with possible UIP (p=0.004). Multivariate analysis showed age, sex, and carbon monoxide diffusing capacity (DLCO) as important independent variables for survival. The UIP HRCT pattern did not affect survival (hazard ratio, 0.83; 95% confidence interval, 0.51-1.24; p=0.32). Possible UIP was not associated with prognosis when independent predictors for survival rate and propensity score were considered. In the case-control study, the 3-year survival rate was 44.6% in the UIP pattern group and 56.8% in the possible UIP group (p=0.16). Clinical characteristics and outcomes were similar in possible UIP and UIP patients, except for differences in DLCO. The UIP pattern itself did not affect survival.

Pulmonary fibrosis and emphysema: Is the emphysema type associated with the pattern of fibrosis?

To investigate whether the predominant emphysema type is associated with the high resolution computed tomography (HRCT) pattern of fibrosis in combined pulmonary fibrosis and emphysema (CPFE). Fifty-three smokers with upper lobe emphysema and lower lobe pulmonary fibrosis on - HRCT - were retrospectively evaluated. Patients were stratified into 3 groups according to the predominant type of emphysema: Centrilobular (CLE), paraseptal (PSE), CLE = PSE. Patients were also stratified into 3 other groups according to the predominant type of fibrosis on HRCT: Typical usual interstitial pneumonia (UIP), probable UIP and nonspecific interstitial pneumonia (NSIP). HRCTs were scored at 5 predetermined levels for the coarseness of fibrosis (Coarseness), extent of emphysema (emphysema), extent of interstitial lung disease (TotExtILD), extent of reticular pattern not otherwise specified (RetNOS), extent of ground glass opacity with traction bronchiectasis (extGGOBx), extent of pure ground glass opacity and extent of honeycombing. HRCT mean scores, pulmonary function tests, diffusion capacity (DLCO) and systolic pulmonary arterial pressure were compared among the groups. The predominant type of emphysema was strongly correlated with the predominant type of fibrosis. The centrilobular emphysema group exhibited a significantly higher extent of emphysema (P < 0.001) and a lower extent of interstitial lung disease (P < 0.002), reticular pattern not otherwise specified (P < 0.023), extent of ground glass opacity with traction bronchiectasis (P < 0.002), extent of honeycombing (P < 0.001) and coarseness of fibrosis (P < 0.001) than the paraseptal group. The NSIP group exhibited a significantly higher extent of emphysema (P < 0.05), total lung capacity (P < 0.01) and diffusion capacity (DLCO) (P < 0.05) than the typical UIP group. The typical UIP group exhibited a significantly higher extent of interstitial lung disease, extent of reticular pattern not otherwise specified, extent of ground glass opacity with traction bronchiectasis, extent of honeycombing and coarseness of fibrosis (0.039 > P > 0.000). Although the pulmonary arterial pressure was higher in typical UIP group relative to the NSIP group, the difference was not statistically significant. In CPFE patients, paraseptal emphysema is associated more with UIP-HRCT pattern and higher extent of fibrosis than centrilobular emphysema.

The difference of neovascularization in early intra‐alveolar fibrosis between nonspecific interstitial pneumonia and usual interstitial pneumonia

Of the idiopathic interstitial pneumonias (IIPs), usual interstitial pneumonia (UIP) and diffuse alveolar damage (DAD) usually have poor prognoses. The prognoses of cryptogenic organizing pneumonia (COP) and nonspecific interstitial pneumonia (NSIP) are usually more favorable. Although several reports have described neovascularization in COP and UIP, this aspect of UIP has not been compared with NSIP. In this study, we evaluated neovascularization in intra-alveolar fibrotic lesion of cases of fibrosing NSIP (f-NSIP) (n = 26) and UIP (n = 25). In the f-NSIP group, a considerable degree of neovascularization was observed compared to the UIP group and bud type intra-alveolar fibrosis showed a greater degree of neovascularization compared to the mural-incorporation and obliterative types of intra-alveolar fibrosis. Real-time reverse transcription polymerase chain reaction revealed a significantly greater expression of VEGF-A mRNA in f-NSIP than in UIP. The expression of matrix metalloproteinase-2 (MMP-2) mRNA also showed significantly higher in f-NSIP than UIP. The greater VEGF-A and MMP-2 expression may play a role in the pathogenesis of neovascularization in early intra-alveolar fibrotic lesions in f-NSIP.

Prognostic significance of fibroblastic foci in usual interstitial pneumonia and non‐specific interstitial pneumonia

Fibroblastic foci (FF) composed of an accumulation of fibroblasts or myofibroblasts may be related to the progression of pulmonary fibrosis leading to respiratory insufficiency. Several studies have shown that the number of FF is a significant prognostic factor in usual interstitial pneumonia (UIP). The purpose of the present study was to examine whether the extent of FF is related to impairment of respiratory function and prognosis in patients with biopsy-proven fibrosing interstitial pneumonia, including UIP and fibrotic non-specific interstitial pneumonia (fNSIP). Fifty patients with histologically confirmed interstitial pneumonia including UIP or fNSIP were investigated, and correlations between FF and pulmonary function were evaluated. FF area was calculated as the proportion of total area (%FF) and the number of FF (FF/cm(2)) in the whole histological specimen from each patient. The UIP group showed significantly higher %FF and FF/cm(2) than the fNSIP group. When UIP and fNSIP patients were analysed together, the group of patients who had died (death group) revealed significantly higher %FF and FF/cm(2) compared with the group of survivors, and the impairment of vital capacity and diffusing capacity of carbon monoxide was correlated with %FF and FF/cm(2). FF correlated with impaired pulmonary function and may be a useful parameter to predict prognosis in patients with UIP and fNSIP.

High-Resolution CT Findings in Fibrotic Idiopathic Interstitial Pneumonias With Little Honeycombing: Serial Changes and Prognostic Implications

This retrospective study evaluates serial changes of lung abnormalities on high-resolution CT (HRCT) and clarifies prognostic determinants among CT findings in fibrotic idiopathic interstitial pneumonias (IIPs) with little honeycombing. We enrolled 154 patients with a histologic diagnosis of a fibrotic IIP (< 5% honeycombing on CT) who were followed clinically for at least 2 years. One hundred one patients had usual interstitial pneumonia (UIP) and 53 had fibrotic nonspecific interstitial pneumonia (NSIP). On baseline CT, the extent and distribution of lung abnormalities were visually assessed, and serial CT scans were evaluated with a follow-up period of at least 6 months (n = 132). Significant differences were noted in the extent of reticulation and ground-glass opacification (GGO) between the UIP and fibrotic NSIP groups (p < 0.001). On serial scans, honeycombing (5% in UIP and 3% in fibrotic NSIP; p = 0.08) and reticulation (3% in UIP and 8% in fibrotic NSIP; p = 0.03) progressed in extent and GGO (-2% in UIP and -10% in fibrotic NSIP; p = 0.009) decreased in extent. Overall extent of lesions increased in UIP (6%) and decreased in NSIP (-4%) (p = 0.04). On univariate and multivariate Cox proportional hazards analysis, the overall extent of parenchymal abnormalities was a prognostic factor predictive of poor survival duration. Even in cases of fibrotic IIP with little honeycombing, serial CT reveals an increase in the extent of honeycombing and reticulation and a decrease in extent of GGO. Overall extent of lung fibrosis on the baseline CT examination appears predictive of survival in fibrotic IIP with little honeycombing.

Lung diseases directly associated with rheumatoid arthritis and their relationship to outcome

The outcome and cause of death of each lung disease directly associated with rheumatoid arthritis (RA-LD) have been poorly investigated. A retrospective study was conducted of 144 patients with RA-LD, in whom the median follow-up period after the initial visit for a respiratory examination was 4.5 yrs. A total of 57 patients were identified with usual interstitial pneumonia (UIP), 31 with bronchiectasis, 16 with nonspecific interstitial pneumonia (NSIP), 11 with bronchiolitis, five with organising pneumonia (OP), five with diffuse alveolar damage (DAD) and 19 with combined disease. The 5-yr survival rates were 36.6% in the UIP group, 87.1% in the bronchiectasis group, 93.8% in the NSIP group, 88.9% in the bronchiolitis group, 60.0% in the OP group and 20.0% in the DAD group. Survival of patients with DAD was worse than that of patients with UIP. Overall, survival of patients with UIP was worse than that of patients with bronchiectasis, NSIP or bronchiolitis. Of the 144 patients, 71 (49.3%) died, of whom 58 (81.7%) died due to respiratory lesions. Of patients with RA-LD, patients with DAD experienced the highest mortality, and the survival of patients with UIP was worse than that of patients with NSIP.