Idiopathic Interstitial Pneumonitis Research Articles

Combination of computed tomography imaging pattern and severity of respiratory failure as factors associated with prognosis for acute exacerbation of idiopathic chronic fibrosing interstitial pneumonia.

The prognosis of idiopathic chronic fibrotic interstitial pneumonitis (CFIP) in patients with acute exacerbation (AE) is variable. We examined whether the imaging pattern on thoracic computed tomography (CT) or the severity of respiratory failure with AE-CFIP is associated with short-term prognosis. Patients admitted to two university hospitals were retrospectively analyzed and divided into derivation and validation cohorts. The distribution of newly appearing parenchymal abnormalities on thoracic CT was classified into peripheral, multifocal, and diffuse patterns. Respiratory failure was defined as severe if a fraction of inspired oxygen ≥ 0.5 was required to maintain percutaneous oxygen saturation ≥ 90% on admission. Factors associated with 90 day-mortality were analyzed using univariate and Cox proportional hazard regression. In 59 patients with AE-CFIP of the derivation cohort, diffuse pattern on CT was associated with higher mortality within 90 days (43%) than peripheral/multifocal pattern (17%, p = 0.03). Additionally, compared with non-severe failure, severe respiratory failure was associated with higher mortality (47% vs. 21%, p = 0.06). Cox proportional hazard regression analysis demonstrated that a combination of diffuse pattern on CT and severe respiratory failure was associated with the poorest prognosis (hazard ratio [HR] 3.51 [interquartile range 1.26-9.80], p = 0.016) in the derivation cohort, which was confirmed in the validation cohort (n = 31, HR 4.30 [interquartile range 1.51-12.2], p = 0.006). The combination of imaging pattern on thoracic CT and severity of respiratory failure was associated with the prognosis of idiopathic AE-CFIP.

Use of antifibrotic drugs in interstitial lung disease

The interstitial lung diseases ILDs are a heterogeneous group of diseases that often lead to progressive fibrosis of the lungs with corresponding functional impairment. With nintedanib, a tyrosinkinase inhibitor and angiokinase inhibitor, as well as pirfenidone, which unfolds its effect among other things by inhibiting the transforming growth factor β, there are currently 2 approved antifibrotic drugs. In the rapidly progressing idiopathic pulmonary fibrosis IPF, the antifibrotic drugs nintedanib and pirfenidone have been established and approved in therapy for several years. The initiation of antifibrotic therapy should be carried out early after diagnosis by multidisciplinary discussion (MDD). In systemic scleroderma with lung involvement nintedanib should be used in the case of relevant fibrosis in addition to immunosuppressive therapy. Recently, nintedanib has also become a new option for the treatment of progressive fibrosing ILDs (PF-ILDs). This describes the course of various disease entities such as connective tissue disease associated ILDs (CTD-ILDs), fibrosing hypersensitivity pneumonitis or fibrosing courses of non-IPF idiopathic interstitial pneumonitis (non-IPF IIPs) that have a corresponding fibrose-related worsening of respiratory symptoms, a deterioration of lung-functioning parameters or a disease progression in CT. Although pirfenidone also shows positive signals for this group of patients in some selected studies, its use in PF-ILD is not yet recommended. In particular, gastrointestinal side effects can occur under therapy with antifibrotic drugs and require a long-term close interdisciplinary connection of patients.

Perioperative Management of Patients with Idiopathic Pulmonary Fibrosis Undergoing Noncardiac Surgery: A Narrative Review.

PurposeThe idiopathic interstitial pneumonias (IIP) constitute a large cohort of the over 200 subtypes of interstitial lung disease (ILD). Idiopathic pulmonary fibrosis (IPF) is the most widely studied, arguably the most severe etiology of ILD and the most common IIP diagnosis. The objective of this narrative review is to outline the current evidence on optimal perioperative management of IPF. PubMed, Embase and Web of Science were analyzed for appropriate peer-reviewed references by utilizing key word search (“interstitial lung disease” OR “idiopathic pulmonary fibrosis” OR “idiopathic interstitial pneumonitis” OR “ILD” OR “IPF” AND “surgery” OR “anesthesia” OR “perioperative”) within the past thirty years (1990-current). Non-English language references were excluded. A total of 205 references were curated by the authors. Eighty-seven consensus statements, clinical trials, retrospective cohort studies or case series met criteria and were incorporated into the findings of this narrative review.ConclusionAfter review, we conclude that complications, dominated by postoperative pulmonary complications, pose a significant barrier to safe perioperative care of patients with IPF. Ensuring that the preoperative IPF patient has been medically optimized is important for minimizing this risk. Initial assessment of the ARISCAT score, pulmonary function studies and cardiopulmonary exercise testing may identify IPF patients at particularly high perioperative pulmonary risk. Identifying IPF patients with 6–12-month declines in DLCO of >15%, V02max <8.3 mL/kg/min, <80% predicted value FVC, a 50-meter reduction in the 6MWT or preoperative home oxygen use may be helpful in preoperative risk stratification. Medically optimizing treatable co-morbidities should be a priority in preoperative assessment. Regional or neuraxial anesthesia should be considered an optimal technique for the avoidance of general anesthesia related complications when indicated. Acute exacerbation and postoperative pneumonia have been identified as important postsurgical complications in both thoracic and nonthoracic surgical populations.

Spectrum of interstitial lung diseases and their association with pulmonary hypertension.

Interstitial lung diseases (ILDs) are an intriguing group of pulmonary disorders, which still require the study of epidemiological, genetic, pathophysiological, clinical, and radiological parameters. Pulmonary hypertension (PH) is an underreported complication in interstitial lung diseases which is associated with worse outcome. In our study, we have reported the spectrum of ILDs and estimated the prevalence of pulmonary hypertension among these subjects at a tertiary care centre. A cross-sectional study was performed in which demographical, clinical, radiological, and histological data of subjects with ILD, attending the department of Respiratory Medicine in the University was collected from 1st September 2018 to 31st August 2019. Serological tests were done wherever indicated. Standard criteria along with multidisciplinary opinion were needed to arrive at the final diagnosis. All subjects were screened for pulmonary hypertension via 2-D echocardiography. Mean pulmonary artery pressure ≥20 mmHg was used to define PH. In the defined period, 239 subjects were enrolled (58% females, n=141; mean age 52.38±13.40 years). A tissue diagnosis was obtained in 34% cases. The most common ILD was hypersensitivity pneumonitis (32.2%), followed by autoimmune-ILD (31.4%), idiopathic pulmonary fibrosis (IPF) (15.9%) and sarcoidosis (12.6%), non-IPF idiopathic interstitial pneumonitis (2.1%) and rest 21 (5.9%) subjects were diagnosed as other types of ILD. Pulmonary hypertension was seen in 46.0% of subjects.

A PUZZLING CASE OF RECURRENT PNEUMONIA: PLEUROPARENCHYMAL FIBROELASTOSIS

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pleuroparenchymal fibroelastosis (PPFE) is a fibroelastic process mainly affecting the visceral pleura and subpleural spaces with a propensity towards the upper lobes. It has unique clinical, pathological and radiological features1. CASE PRESENTATION: An 80 year old female with history of recurrent pneumonias and remote granulomatous disease presented with progressive dyspnea and fatigue. She denied other symptoms including chronic cough or sputum production or fever or chills. Chest X-ray showed extensive parenchymal and pleural fibrotic changes of the upper lobes. Pulmonary function tests suggested a restrictive pattern with reduced diffusion capacity (DLCO). Echocardiogram showed no significant abnormalities. Serial CT scans of the chest done over two years showed worsening pleuroparenchymal fibrotic changes of the upper lobes in a pattern very consistent with PPFE, with no evidence of honeycombing. This was likely idiopathic but potentially related to prior pneumonias and felt less likely to be related to her remote minimal parakeet exposure associated hypersensitivity pneumonitis. Her ANA titers were mildly elevated at 1:160 but further workup for auto-antibodies were negative including RF and CCP antibodies. ESR and CRP were minimally elevated. A bronchoscopy was offered to evaluate for infectious or other etiologies but she opted to wait. Her CT findings were however very consistent with PPFE and a provisional diagnosis of the same was made. DISCUSSION: PPFE is a rare but under-diagnosed type of interstitial lung disease. It is mostly idiopathic in nature but sometimes occurs as a late complication after lung transplantation. Although similar findings may be sometimes described in patients with autoimmune or connective tissue disease, it usually presents as a late complication and in certain patients with hypersensitivity pneumonitis, the idiopathic ones are best classified as PPFE1. PPFE is mostly seen in patients aged 40 to 70 years and presents as progressive dyspnea with or without cough. PPFE has to be differentiated from other upper lobe diseases like hypersensitivity pneumonia, sarcoidosis, idiopathic interstitial pneumonitis, non-tuberculous mycobacterial infection, pneumoconiosis, malignancy and apical pleural cap. High resolution CT scan remains the best diagnostic modality to show diffuse fibroelastic process predominantly affecting pleura and upper lobe parenchyma1. Pulmonary function test shows a restrictive pattern with reduced DLCO. No specific laboratory tests are diagnostic2. Surgical biopsies although not required for diagnosis can demonstrate intra-alveolar fibrosis and elastosis2. CONCLUSIONS: The prognosis of PPFE remains poor as no treatment is proven to be effective except therapeutic lung transplantation1. Further studies to understand pathogenesis, diagnostic markers and treatment modalities for this rare progressive disease are much warranted. REFERENCE #1: Chua F, Desai SR, Nicholson AG, et al. Pleuroparenchymal fibroelastosis. A review of clinical, radiological and pathological characteristics. Ann Am Thorac Soc 2019;16:1351-9. REFERENCE #2: Reddy TL, Tominaga M, Hansell DM, von der Thusen J, Rassl D, Parfrey H, Guy S, Twentyman O, Rice A, Maher TM, Renzoni EA, Wells AU, Nicholson AG. Pleuroparenchymal fibroelastosis: a spectrum of histopathological and imaging phenotypes. Eur Respir J. 2012 Aug;40(2):377-85. DISCLOSURES: No relevant relationships by Ansaam Daoud, source=Web Response No relevant relationships by Palak Rath, source=Web Response No relevant relationships by Lokesh Venkateshaiah, source=Web Response

National Registry of Interstitial Lung Disease from Pakistan.

IntroductionInterstitial lung disease (ILD) is a heterogeneous group of over 200 parenchymal lung diseases with a myriad of etiologies. Interstitial lung disease registries from around the world show varying prevalence and incidence of these diseases. The aim of this study was to determine the epidemiology and characteristics of ILD in Pakistan.MethodsThis web-based registry, which is the first multicenter registry of ILD from Pakistan, recruited patients from 10 centers of five major cities between January 2016 and March 2019.ResultsA total of 744 patients were enrolled in the registry. The five most frequent ILDs were idiopathic pulmonary fibrosis (IPF) 34.4%, hypersensitivity pneumonitis (HP) - 17.7%, idiopathic nonspecific interstitial pneumonitis (iNSIP) - 16.8%, connective tissue disease-associated ILD (CTD-ILD) - 16.3%, and sarcoidosis - 9.1%.ConclusionIdiopathic pulmonary fibrosis is the most prevalent ILD in Pakistan, followed by HP and iNSIP. An ongoing prospective registry with longitudinal follow-up will help us further elaborate on the clinical characteristics, treatment, and survival outcome of patients with ILD.

Multidisciplinary team obviates biopsy in most patients with diffuse parenchymal lung diseases—A retrospective study from India

The inflammation and fibrosis in diffuse parenchymal lung diseases (DPLDs) in varied proportions give rise to different patterns in radiology and histopathology. The radiological pattern on CT of the thorax most often allows us to make a diagnosis with varying levels of confidence, to optimize management. With a multidisciplinary team bringing the strengths of their individual domains of knowledge, clinical, radiological, histopathological, and in many cases rheumatological, the level of confidence in making this diagnosis increases, often to the stage where the diagnosis is most often right, is concordant with the diagnosis achieved at histopathology and therefore obviates the need for lung biopsy which carries its own costs and risks of complications. Our study emphasizes the role of the multidisciplinary team (MDT) in the management of DPLDs at a tertiary care referral center. Every case of DPLD presenting to our pulmonology department was discussed in an MDT meeting before subjecting them to any diagnostic intervention or therapy. A clinico-radiological diagnosis was made according to the 2002 ATS/ERS guidelines initially. Later an official ATS/ERS/JRS/ALAT statement on idiopathic pulmonary fibrosis and a 2013 ATS/ERS consensus for the classification and diagnosis of idiopathic interstitial pneumonia was used. The concordance in our study was defined as the percentage of histopathological diagnoses that were identical to the clinico-radiological MDT diagnosis prior to the biopsy. A total of 434 patients with DPLDs were evaluated. The MDT suggested biopsy for only 38.7% (168/434) patients since the pattern was very clear in 266 (61.3%) cases. As not all patients consented to undergo the biopsy procedure when recommended, histopathology was obtained in 102 patients. The histological diagnosis was concordant with the initial MDT diagnosis in 80.3% (82/102) of samples. On an individual basis, connective tissue disease-interstitial lung disease and sarcoidosis showed the best concordance (87%). In idiopathic non-specific interstitial pneumonitis (NSIP) cases, the histopathological diagnosis concurred in only 53.3% (8/15), out of which 8 were NSIP, 4 were usual interstitial pneumonia, and 3 were reported as inadequate sampling on histopathology. The MDT plays a crucial role in the diagnosis of DPLDs. Not every pattern requires biopsy confirmation. However, an idiopathic non-specific interstitial pneumonitis diagnosis by the MDT should probably be better confirmed by biopsy.

Determining the incidence of interstitial pneumonitis and chronic kidney disease following full intensity haemopoetic stem cell transplant conditioned using a forward-planned intensity modulated total body irradiation technique

Purpose/ObjectiveTotal body irradiation (TBI) remains a key component of conditioning for allogeneic haemopoietic stem cell transplant (HSCT), with interstitial pneumonitis (IP) and chronic kidney disease (CKD) important late sequelae. We undertook a retrospective service evaluation of TBI patients treated with a forward-planned intensity modulated radiotherapy technique (FP IMRT). Material/Methods74 adult patients were identified; all received step and shoot FP IMRT TBI, 14.4 Gy in 8 fractions over 4 days. Mean doses to the lungs and kidneys were 12–12.5 Gy. Toxicities were defined as per CTCAE v4.0: IP as multilobar infiltrates on CT with symptoms of dyspnoea, and renal dysfunction as an Estimated Glomerular Filtration rate (eGFR) < 60 ml/min/1.73 m2 for > 3 months. Secondary endpoints were overall survival (OS), progression free survival (PFS), cumulative incidence of non-relapse mortality (NRM), relapse risk and of acute and chronic GvHD. ResultsPatients received treatment for the following diagnosis: ALL/LBL (n = 37); AML (n = 33), CML-BC (n = 2) and High grade NHL (n = 2). The rate of IP due to any cause was 30%; positive microbiological evidence in 73% (16 /22). Idiopathic IP was seen in 8%, with only 4% (n = 3) having IP Grade ≥ 3.Two (4%) of 52 long term survivors developed CKD, one with thrombotic microangiopathy.4 year NRM was 16% (CI 11–32%); no treatment related deaths in matched sibling or umbilical cord blood HSCT. ConclusionFP IMRT TBI, reducing dose to the lungs and kidneys, has lower rates of idiopathic IP and CKD compared to the literature. This technique is safe and effective conditioning for full intensity HSCT.

Interaction between the promoter MUC5B polymorphism and mucin expression: is there a difference according to ILD subtype?

The MUC5B promoter variant rs35705950 is associated with idiopathic pulmonary fibrosis (IPF). MUC5B glycoprotein is overexpressed in IPF lungs. We examined immunohistochemical expression of MUC5B in different interstitial lung disease...

Asbestos-related diseases.

Knowledge of asbestos-related diseases has been accumulating for over one hundred years as the industrial value of asbestos was recognised for the strength of its fibres and their resistance to destruction, resulting in increasing production and use until the multiple health effects have become apparent. Deposition in the lung parenchyma results in an inflammatory/progressively fibrotic response, with impaired gas exchange and reduced lung compliance ('asbestosis'), causing progressive dyspnoea and respiratory failure for which only palliation is indicated, although anti-fibrotic agents used for idiopathic usual interstitial pneumonitis remain to be evaluated. Benign pleural effusion, diffuse pleural fibrosis (occasionally with associated rolled atelectasis) and pleural plaques are the non-malignant pleural diseases that result from fibres reaching the pleura. But the main issues that led to the ban on asbestos in industry are those of malignancy: lung cancer, malignant mesothelioma (MM) of the pleura and MM of the peritoneum. Bronchogenic carcinoma risk from asbestos exposure is dose-dependent and multiplies the risk attributable to tobacco smoking. The principles of treatment are as for all cases of lung cancer. Low-dose computed tomography screening of exposed people can detect early-stage, non-small cell cancers, with improved survival. The amphibole varieties of asbestos are much more potent causes of MM than chrysotile, and the risk increases exponentially for 40-50 years following first exposure. As MM is non-resectable and poorly responsive to chemotherapy and radiotherapy, curative treatment is not possible and screening not justified.

Lung transplantation in China between 2015 and 2018.

Lung transplantation (LT) has been demonstrated as the only effective therapy for patients with end-stage lung diseases. Increasing listed lung transplant candidates and expanding volumes of lung transplant centers across China require well-organized programs and registry data collection based on the large population. This study aimed to summarize and analyze the data of LT development in China. We retrospectively collected and analyzed data from the China Lung Transplantation Registry (CLuTR). Key data were reported from the registry with transplant types, indications, donor and recipient characteristics, outcomes and survival. The survival <30 days, 1-year and 3-year survival rates were estimated with risk factors identified. CLuTR contained data from 1053 lung transplants performed through January 1st, 2015 to December 31st, 2018 reported by 18 registered transplant centers. The largest category of diagnosis before transplantation was idiopathic interstitial pneumonitis. The total <30 days, 1-year and 3-year survival rates in CLuTR were 81.45%, 70.11%, and 61.16% with discrepancy by indications. Large proportion of recipients who were more than 60 years old required higher standard of care. Infection-related complications resulted in more death events in the early post-surgery periods. New York Heart Association grading at listing, extra-corporeal membrane oxygenation usage peri-transplantation, allograft dysfunction (primary graft dysfunction >Grade 0), renal insufficiency (estimated glomerular filtration rate <60 mL·min·1.73 m), were independently associated with a higher risk for 3-year mortality in the entire cohort. Facing more end-stage of lung diseases and comorbidities, this study analyzed the outcomes and survival of LT recipients in China. Further prospectively stratified analyses with longer follow-up will be needed.

The case of idiopathic pleuroparenchymal fibroelastosis diagnosed by transbronchial biopsy

Pleuroparenchymal fibroelastosis (PPFE) is claasified in idiopathic interstitial pneumonitis group is rarely seen. Etiology and pathophysiology of this entity are not completely understood. The prognosis is poor, and there is no effective treatment except for lung transplantation. Here, we presented a case of PPFE diagnosed by transbronchial biopsy through fiberoptic bronchoscopy and its histopathological and clinicoradiological features.

Reduced incidence of interstitial pneumonitis after allogeneic hematopoietic stem cell transplantation using a modified technique of total body irradiation.

Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI). Patients who received a TBI-based myeloablative conditioning regimen between 1995 and 2014 were recruited consecutively. Before March 2007, TBI was delivered using Co-TBI (n = 181); afterward, TBI was administered using IM-TBI (n = 126). Forty-four patients developed IP; of these cases, 19 were idiopathic. The IP-related mortality rate was 50% in the total IP cohort and 63% in the idiopathic subgroup. The 1-year cumulative incidences of IP and idiopathic IP were 16.5% and 7.4%, respectively; both rates were significantly higher in the Co-TBI group than in the IM-TBI group. Multivariate analysis revealed that Co-TBI was an independent prognostic factor for both total and idiopathic IP. In the acute myeloid leukemia subgroup, patients with different TBI techniques had similar outcomes for both overall and relapse-free survival. In conclusion, IM-TBI is an easy and effective TBI technique that could substantially reduce the complication rate of IP without compromising treatment efficacy.

αvβ6 integrin may be a potential prognostic biomarker in interstitial lung disease

Idiopathic pulmonary fibrosis (IPF) and fibrotic nonspecific interstitial pneumonitis are progressive interstitial lung diseases (ILDs) with limited treatment options and poor survival. However, the rate of disease progression is variable, implying there may be different endotypes of disease. We hypothesised that immunophenotyping biopsies from ILD patients might reveal distinct endotypes of progressive fibrotic disease, which may facilitate stratification when undertaking clinical trials of novel therapies for IPF.43 paraffin-embedded, formalin-fixed lung tissue sections were immunostained for five molecules implicated in the pathogenesis of the fibrosis: α-smooth muscle actin (αSMA), αvβ6 integrin, pro-surfactant protein C (SP-C), hepatocyte growth factor (HGF) and tenascin-C (TenC). Levels of immunostaining and numbers of fibroblastic foci were quantified using operator-dependent and -independent methods. The relationship of all these markers to overall survival was analysed.Staining revealed high levels of αSMA, αvβ6 integrin, pro-SP-C, HGF and TenC, and fibroblastic foci. Immunostaining varied across samples for all molecules but only the extent of αvβ6 integrin immunostaining was associated with increased mortality. There was no association with the other markers measured.Our data suggest high levels of αvβ6 integrin may identify a specific endotype of progressive fibrotic lung disease.

MMP-7 and fcDNA Serum Levels in Early NSCLC and Idiopathic Interstitial Pneumonia: Preliminary Study

A non-invasive test to facilitate the diagnosis of non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF) is still not available and represents an important goal. Forty-eight patients with stage I NSCLC, 45 with IPF, 30 with other idiopathic interstitial pneumonias (IIPs) including idiopathic non-specific interstitial pneumonia (NSIP) and chronic hypersensitivity pneumonitis (HP), 35 with diffuse non-malignant disease and 30 healthy donors were enrolled onto the study. Free circulating (fc)DNA and MMP-7 levels were evaluated by Real Time PCR and ELISA, respectively. Median fcDNA levels were similar in NSCLC (127 ng/mL, range 23.6–345 ng/mL) and IPF (106 ng/mL, range 22–224 ng/mL) patients, and significantly lower in IIPs patients, in individuals with other diseases and in healthy donors (p < 0.05). Conversely, median MMP-7 values were significantly higher in IPF patients (9.10 ng/mL, range 3.88–19.72 ng/mL) than in those with NSCLC (6.31 ng/mL, range 3.38–16.36 ng/mL; p < 0.0001), NSIP (6.50 ng/mL, range 1.50–22.47 ng/mL; p = 0.007), other diseases (5.41 ng/mL, range 1.78–15.91, p < 0.0001) or healthy donors (4.35 ng/mL, range 2.45–7.23; p < 0.0001). Serum MMP-7 levels seem to be capable of distinguishing IPF patients from those with any other lung disease. fcDNA levels were similar in NSCLC and IPF patients, confirming its potential role as a biomarker, albeit non-specific, for the differential diagnosis of NSCLC.

Pulmonary Manifestations of Collagen Diseases

Collagen diseases are a large group of systemic inflammatory diseases of autoimmune etiology. The etiopathogenesis of collagen diseases is multifactorial. There is genetic susceptibility, as many connective tissue disorders show family history, and environmental factors may trigger the disease. Collagen diseases can affect almost all the organs of the body. The respiratory system is one of the most frequently affected, although the prevalence of pulmonary disease is not precisely known for the different collagen disorders. Any structure of the respiratory tract can be affected, but perhaps the most frequent is pulmonary parenchymal disease in the form of pneumonitis, which can be produced in any of the idiopathic interstitial pneumonitis patterns. The pleura, pulmonary vessels, airways and respiratory muscles may also be affected. The frequency of lung disease associated with collagen diseases is on the rise. This is in due part to the better diagnostic methods that are available to us today (such as high-resolution computed tomography) and also to the appearance of new forms of pneumonitis associated with the new treatments that are currently used. The objective of this article is to offer a global vision of how collagen diseases can affect the lungs according to the latest scientific evidence.

Manifestaciones pulmonares de las enfermedades del colágeno

Collagen diseases are a large group of systemic inflammatory diseases of autoimmune etiology. The etiopathogenesis of collagen diseases is multifactorial. There is genetic susceptibility, as many connective tissue disorders show family history, and environmental factors may trigger the disease. Collagen diseases can affect almost all the organs of the body. The respiratory system is one of the most frequently affected, although the prevalence of pulmonary disease is not precisely known for the different collagen disorders. Any structure of the respiratory tract can be affected, but perhaps the most frequent is pulmonary parenchymal disease in the form of pneumonitis, which can be produced in any of the idiopathic interstitial pneumonitis patterns. The pleura, pulmonary vessels, airways and respiratory muscles may also be affected. The frequency of lung disease associated with collagen diseases is on the rise. This due in part to the better diagnostic methods that are available to us today (such as high-resolution computed tomography) and also to the appearance of new forms of pneumonitis associated with the new treatments that are currently used. The objective of this article is to offer a global vision of how collagen diseases can affect the lungs according to the latest scientific evidence.

Current Status of Idiopathic Nonspecific Interstitial Pneumonia

Pulmonary pathologists were aware of cases of idiopathic interstitial pneumonia (IIP) that morphologically did not fit Liebow's classification scheme. These cases were labeled as "cellular interstitial pneumonia" or "chronic interstitial pneumonia not otherwise specified." The term nonspecific interstitial pneumonia (NSIP) was first used in relation to a pattern of lung interstitial inflammation seen in association with human immunodeficiency virus (HIV) infection. In 1994 NSIP was used to indicate a group of subacute or chronic interstitial pneumonias characterized morphologically by interstitial inflammation or fibrosis or both, with preservation of the lung architecture and the absence of typical findings for any of the other main categories of IIP (mainly usual interstitial pneumonia, desquamative interstitial pneumonia, and bronchiolitis obliterans organizing pneumonia). Although these patients presented with "nonspecific" lung histology (categorized as cellular and fibrotic variants), and with a broad spectrum of associated clinical conditions, such as connective tissue diseases (CTDs), environmental exposure, and previous acute lung injury, they showed some peculiar clinical aspects, including favorable response to corticosteroid treatment and overall good prognosis.The clinical and radiographic profiles were better defined in the last decade. The NSIP pattern is the histological background of a subacute/chronic interstitial pneumonitis that may be observed in many conditions, including CTD, drug-induced lung disease, hypersensitivity pneumonitis, slowly healing diffuse alveolar damage (DAD), relapsing organizing pneumonia, occupational exposure, immunodeficiency (mainly HIV infection), graft versus host disease (GVHD), familial pulmonary fibrosis, immunoglobulin G4 (IgG4)-related sclerosing disease, with or without overlap features with Rosai-Dorfman disease, multicentric Castleman disease, and myelodysplastic syndrome. Rarely, NSIP is the histology recognized in patients with idiopathic interstitial pneumonitis, in whom efforts to find potential causative exposures are futile. This entity occurs mostly in middle-aged, never-smoker women, with a likely association with an autoimmune background. High-resolution computed tomographic (HRCT) scans typically demonstrate ground-glass attenuation with a bibasilar distribution, or in the fibrotic variant, ground-glass attenuation along with reticular lines and traction bronchiectasis. The prognosis is good compared with idiopathic pulmonary fibrosis (IPF), and therapeutic options include mainly corticosteroids and immunosuppressive agents. Recently a more precise definition of clinical profiles and radiographic findings of idiopathic NSIP allows consideration of less invasive diagnostic procedures (bronchoalveolar lavage, transbronchial lung biopsy). Better understanding of pathogenetic mechanisms might widen the therapeutic horizon giving a role to new therapeutic options in more severe cases.

Comparative manifestations and diagnostic accuracy of high-resolution computed tomography in usual interstitial pneumonia and nonspecific interstitial pneumonia

Of the idiopathic interstitial pneumonias, the differentiation between idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonitis (NSIP) raises considerable diagnostic challenges, as their clinical presentations share many overlapping features. IPF is a fibrosing pneumonia of unknown cause, showing a histologic pattern of usual interstitial pneumonia (UIP), and has a poorer prognosis than does NSIP. This review examines whether the radiographic features of IFP and NSIP as assessed by high-resolution computed tomography (HRCT) can be used to distinguish between these two entities. The diagnostic accuracy of HRCT for UIP and NSIP has been reported to be approximately 70% in various studies. Disagreement between the HRCT diagnosis and the histologic diagnosis occurs in approximately one-third of the cases. The predominant feature of honeycombing on HRCT yields a specificity of approximately 95% and sensitivity of approximately 40% for UIP. In contrast, a predominant feature of ground glass opacities (GGOs) gives a sensitivity of approximately 95% and specificity of approximately 40% for NSIP. The finding of honeycombing as the predominant HRCT feature suggests the diagnosis of UIP and may exclude the need for biopsy. Predominant features of GGOs are not specific enough to distinguish between NSIP and UIP.

Correlation between circulating fibrocytes, and activity and progression of interstitial lung diseases

Interstitial lung diseases (ILD) are characterized by progressive interstitial pulmonary fibrosis and a decline in lung function. Fibrocytes are bone marrow-derived mesenchymal progenitor cells that may play a role in the pathogenesis of pulmonary fibrosis. Circulating fibrocyte numbers have been correlated with the prognosis of patients with idiopathic pulmonary fibrosis. The aim of the present study was to evaluate the relationship between circulating fibrocytes, and parameters of disease activity and progression in several groups of patients with ILD. The study population comprised 41 patients with ILD and seven healthy control subjects. Circulating CD45(+) collagen-I(+) fibrocytes were evaluated by flow cytometry. The number of circulating fibrocytes was significantly increased in all patients with ILD and particularly in patients with idiopathic interstitial pneumonitis and interstitial pneumonitis associated with collagen vascular disease as compared with healthy control subjects. The numbers of circulating fibrocytes were significantly correlated with pulmonary function test parameters and with serum levels of sialylated carbohydrate antigen, a marker of disease activity. Temporal changes in circulating fibrocyte numbers were evaluated in two patients, and the results suggested that these changes correlated with the activity of ILD. The results from this study provide further evidence for the role of circulating fibrocytes in fibrotic lung diseases.