Update of the guidelines for the pharmacological treatment of rheumatoid arthritis by the Mexican College of Rheumatology 2023.

OBJECTIVE: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA). METHODS: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process. RESULTS: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others. CONCLUSIONS: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients.

The type 2 inflammatory response favors recognition of tumor antigens by IgE in breast cancer.

BACKGROUND: Several studies describe an inverse statistical relationship between the presence of an allergy and development of cancer. However, the immunological mechanism involved in the relationship between these two degenerative diseases has not been explored. AIMS: The main objective of this study was to explore the possibility that the lymphocyte T helper (Th) 2 response, a characteristic of allergy, induces recognition of tumor antigens. METHODS AND RESULTS: Patients with a clinical diagnosis of breast ductal carcinoma were included. Histopathological markers related to proliferation of tumor cells were determined (Her-2-neu, Ki-67, estrogen receptor, and progesterone receptor). IHC was performed using IgE antibodies purified from an allergy patient and from each biopsy donor patient. Serum concentrations of cytokines representative of Th1 and Th2 inflammatory responses were determined. A total of 14 patients with a confirmed diagnosis of breast ductal carcinoma were included. IHC performed on biopsies showed a weak response when using purified IgE antibodies from an allergy patient; however, IHC using the IgE of each patient as the primary antibody showed an intense and highly specific signal. Serum concentrations of cytokines of the Th2 response, that is, IL-4 (130.5 pg/mL (116-135 pg/mL)), IL-5 (202 pg/mL (191-213 pg/mL)), and IL-13 (105.5 pg/mL (98-117 pg/mL)), were significantly higher than those of the Th1 response, that is, IL-6 (86 pg/mL (79-90 pg/mL)) and INF-γ (93 pg/mL (79-99 pg/mL)). CONCLUSION: Purified IgE antibodies specifically recognize tumor cells in breast ductal carcinoma.

Peptidyl Arginine Deiminases in Chronic Diseases: A Focus on Rheumatoid Arthritis and Interstitial Lung Disease.

Protein citrullination is accomplished by a broad enzyme family named Peptidyl Arginine Deiminases (PADs), which makes this post-translational modification in many proteins that perform physiological and pathologic mechanisms in the body. Due to these modifications, citrullination has become a significant topic in the study of pathological processes. It has been related to some chronic and autoimmune diseases, including rheumatoid arthritis (RA), interstitial lung diseases (ILD), multiple sclerosis (MS), and certain types of cancer, among others. Antibody production against different targets, including filaggrin, vimentin, and collagen, results in an immune response if they are citrullinated, which triggers a continuous inflammatory process characteristic of autoimmune and certain chronic diseases. PAD coding genes (PADI1 to PADI4 and PADI6) harbor variations that can be important in these enzymes' folding, activity, function, and half-life. However, few studies have considered these genetic factors in the context of chronic diseases. Exploring PAD pathways and their role in autoimmune and chronic diseases is a major topic in developing new pharmacological targets and valuable biomarkers to improve diagnosis and prevention. The present review addresses and highlights genetic, molecular, biochemical, and physiopathological factors where PAD enzymes perform a major role in autoimmune and chronic diseases.

TNFRSF1B and TNF Variants Are Associated With Differences in Levels of Soluble Tumor Necrosis Factor Receptors in Patients With Severe COVID-19.

BACKGROUND: The impact of genetic variants in the expression of tumor necrosis factor-α (TNF-α) and its receptors in coronavirus disease 2019 (COVID-19) severity has not been previously explored. We evaluated the association of TNF (rs1800629 and rs361525), TNFRSF1A (rs767455 and rs1800693), and TNFRSF1B (rs1061622 and rs3397) variants with COVID-19 severity, assessed as invasive mechanical ventilation (IMV) requirement, and the plasma levels of soluble TNF-α, TNFR1, and TNFR2 in patients with severe COVID-19. METHODS: The genetic study included 1353 patients. Taqman assays were used to assess the genetic variants. ELISA was used to determine soluble TNF-α, TNFR1, and TNFR2 in plasma samples from 334 patients. RESULTS: Patients carrying TT (TNFRSF1B rs3397) exhibited lower PaO2/FiO2 levels than those with CT + CC genotypes. Differences in plasma levels of TNFR1 and TNFR2 were observed according to the genotype of TNFRSF1B rs1061622, TNF rs1800629, and rs361525. According to the studied genetic variants, there were no differences in the soluble TNF-α levels. Higher soluble TNFR1 and TNFR2 levels were detected in patients with COVID-19 requiring IMV. CONCLUSIONS: Genetic variants in TNF and TNFRSFB1 influence the plasma levels of soluble TNFR1 and TNFR2, implicated in COVID-19 severity.

Defining anti-synthetase syndrome: a systematic literature review.

OBJECTIVES: Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated classification criteria are necessary to improve recognition and prevent misclassification, especially given the lack of reliable and standardised autoantibody testing. We systematically reviewed the literature to analyse proposed ASSD criteria, characteristics, and diagnostic performance. METHODS: We searched PubMed and Embase databases (01/01/1984 to 06/11/2018) and the ACR and EULAR meeting abstracts (2017-2018). Sensitivities, specificities, positive, negative likelihood ratios and risk of bias were calculated for ASSD criteria and key variables reported in the literature. We performed meta-analysis when appropriate. RESULTS: We retrieved 4,358 studies. We found 85 proposed ASSD criteria from a total of 82 studies. All but one study included anti-synthetase autoantibody (ARS) positivity in the ASSD criteria. Most studies required only one ASSD feature plus anti-ARS to define ASSD (n=64, 78%), whereas 16 studies required more than one ASSD variable plus anti-ARS. The only criteria not including anti-ARS positivity required 5 ASSD clinical features. We found limited data and wide variability in the diagnostic performance of each variable and definition proposed in the literature. Given these limitations we only meta-analysed the performance of individual muscle biopsy and clinical variables in diagnosing ASSD, which performed poorly. CONCLUSIONS: The current ASSD criteria include a variety of serological, clinical, and histological features with wide variability amongst proposed definitions and the performance of these definitions has not been tested. This systematic literature review suggests the need for additional data and consensus-driven classification criteria for ASSD.

MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression.

BACKGROUND: The major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD. METHODS: Through an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline. RESULTS: Out of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern. CONCLUSION: In this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.

The clinical phenotype of systemic sclerosis patients with anti-PM/Scl antibodies: results from the EUSTAR cohort.

OBJECTIVE: To evaluate clinical associations of anti-PM/Scl antibodies in patients with SSc in a multicentre international cohort, with particular focus on unresolved issues, including scleroderma renal crisis (RC), malignancies, and functional outcome of interstitial lung disease (ILD). METHODS: (1) Analysis of SSc patients from the EUSTAR database: 144 anti-PM/Scl+ without SSc-specific autoantibodies were compared with 7202 anti-PM/Scl-, and then to 155 anti-Pm/Scl+ with SSc-specific antibodies. (2) Case-control study: additional data were collected for 165 anti-PM/Scl+ SSc patients (85 from the EUSTAR registry) and compared with 257 anti-PM/Scl- SSc controls, matched for sex, cutaneous subset, disease duration and age at SSc onset. RESULTS: Patients with isolated anti-PM/Scl+, as compared with anti-Pm/Scl-, had higher frequency of muscle involvement, ILD, calcinosis and cutaneous signs of DM, but similar frequency of SRC and malignancies (either synchronous with SSc onset or not). The presence of muscle involvement was associated with a more severe disease phenotype. Although very frequent, ILD had a better functional outcome in cases than in controls. In patients with both anti-PM/Scl and SSc-specific antibodies, a higher frequency of typical SSc features than in those with isolated anti-PM/Scl was observed. CONCLUSION: The analysis of the largest series of anti-PM/Scl+ SSc patients so far reported helps to delineate a specific clinical subset with muscle involvement, cutaneous DM, calcinosis and ILD characterized by a good functional outcome. SRC and malignancies do not seem to be part of this syndrome.

Anti-HLA Class II Antibodies Correlate with C-Reactive Protein Levels in Patients with Rheumatoid Arthritis Associated with Interstitial Lung Disease.

The pathogenesis of Rheumatoid Arthritis (RA) is not fully understood, probably influenced by genetic and environmental factors. Interstitial Lung Disease (ILD) is an extra-articular manifestation of RA, which contributes significantly to morbidity and mortality. The identification of anti-HLA antibodies has been useful in the transplantation field; however, its contribution to autoimmune diseases as RA has not been fully studied. We aimed to determine the presence of anti-HLA antibodies in RA patients with and without ILD and its possible association with clinical and biochemical markers. One-hundred and forty-seven RA patients, of which 65 had ILD (RA-ILD group), were included. Sera samples for Anti-HLA Class II LABScreen panel-reactive antibodies (PRA) were analyzed. In both groups, women predominated, and lung function was worse in patients with ILD. The anti-CCP+ (UI/mL) was higher in the RA group in comparison to RA-ILD (p < 0.001). Expositional risk factors (tobacco smoking and biomass-burning smoke) were higher in RA-ILD patients. PRA+ was identified in ~25% RA-ILD patients, while ~29% in the RA group. The CRP levels have a positive correlation with the percentage of reactivity (%PRA, p = 0.02, r2 = 0.60) in the RA-ILD group. In conclusion, anti-HLA antibodies correlate with C-reactive protein levels in RA patients with ILD.

An Open-label Study With Pirfenidone on Chronic Hypersensitivity Pneumonitis.

BACKGROUND: Chronic hypersensitivity pneumonitis (cHP) represents a severe lung disease often evolving to fibrosis with the subsequent destruction of the lung parenchyma. There are no approved therapies with confirmed efficacy to deal with this disease. METHODS: We performed an open-label, proof of concept study, to evaluate the efficacy and safety of pirfenidone added to immunosuppressive drugs on the treatment of cHP. We included 22 patients assigned to two groups: Group 1, nine patients that received prednisone plus azathioprine and Group 2, thirteen patients, received prednisone plus azathioprine and pirfenidone (ClinicalTrials.gov identifier NCT02496182). There were no significant imbalances in clinically relevant baseline characteristics between two study groups. RESULTS: After 1 year of treatment, inclusion of pirfenidone was not associated with improved forced vital capacity (primary end-point). A not significant tendency to show higher improvement of diffusion capacity of the lung for carbon monoxide (DLCO) was observed in the group receiving pirfenidone (p=0.06). Likewise, a significant improvement in the total score on the SGRQ was found in the group 2 (p=0.02) without differences in other two questionnaires related to quality of life (ATAQ-IPF and EQ-5D-3L). HRCT showed a decrease of the ground glass attenuation without changes in the fibrotic lesions and without differences between both groups. CONCLUSIONS: These findings suggest that the addition of pirfenidone to the anti-inflammatory treatment in patients with chronic HP may improve the outcome with acceptable safety profile. However, prospective randomized double-blind, placebo-controlled trials in largest cohorts are needed to validate its efficacy.

MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease.

BACKGROUND: Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA. METHODS: Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls. RESULTS: Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7×10-17). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7×10-35) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3×10-49). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4×10-5), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5×10-6). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone. CONCLUSIONS: We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Société Française de Rhumatologie and others.).

Increased histopathological yield for granulomatosis with polyangiitis based on nasal endoscopy of suspected active lesions.

PURPOSE: To present the results of an endoscopic and histopathologic evaluation of suspected nasal active granulomatosis with polyangiits (GPA) lesions, describe them as seen by the ENT specialist, and propose a guide for tissue sampling of the nasal cavity to improve the yield of confirmatory histology. METHODS: Randomly selected patients seen from December 1997-October 2007 had a thorough endoscopic nasal evaluation, preceded by careful cleansing of the nasal cavity. Endoscopic lesions were described; sensitivities, specificities, and predictive values of the composites of endoscopic and histological activity were determined. RESULTS: Six lesions, some not previously described in detail, were observed: white submucosal nodules, mucosal swelling, polypoid nodules, vascular submucosal dilatations, bloody submucosal patches, and ulcers. Of these, polypoid nodules (PPV 100%), persistent white submucosal nodules (PPV 81%), and bloody submucosal patches (PPV 93%) had the better diagnostic performance with confirmed histological diagnosis. CONCLUSIONS: Careful nasal cavity preparation, observation, and description of the nasal mucosa can guide tissue sampling documenting active GPA. This can lead to a better histological yield when definitive proof of the disease is needed.

Economic impact of expanded use of biologic therapy for the treatment of rheumatoid arthritis and Crohn's disease in Argentina, Brazil, Colombia, and Mexico.

OBJECTIVES: To estimate economic impact resulting from increased biologics use for treatment of rheumatoid arthritis (RA) and Crohn's disease (CD) in Argentina, Brazil, Colombia, and Mexico. METHODS: The influence of increasing biologics use for treatment of RA during 2012-2022 and for treatment of CD during 2013-2023 was modeled from a societal perspective. The economic model incorporated current and projected medical, indirect, and drug costs and epidemiologic and economic factors. Costs associated with expanded biologics use for RA were compared with non-expanded use in Argentina, Brazil, Colombia, and Mexico. A similar analysis was conducted for CD in Brazil, Colombia, and Mexico. RESULTS: Accounting for additional costs of biologics and medical and indirect cost offsets, the model predicts that expanded use of biologics for patients with RA from 2012 to 2022 will result in cumulative net cost savings of ARS$2.351 billion in Argentina, R$9.004 billion in Brazil, COP$728.577 billion in Colombia, and MXN$18.02 billion in Mexico; expanded use of biologics for patients with CD from 2013 to 2023 will result in cumulative net cost savings for patients with CD of R$0.082 billion in Brazil, COP$502.74 billion in Colombia, and MXN$1.80 billion in Mexico. Indirect cost offsets associated with expanded biologics use were a key driver in reducing annual per-patient net costs for RA and CD. LIMITATIONS: Future economic projections are limited by the potential variance between projected and actual future values of biologic prices, wages, medical costs, and gross national product for each country. CONCLUSIONS: Increasing biologics use to treat RA and CD may limit cost growth over time by reducing medical and indirect costs. These findings may inform policy decisions regarding biologics use in Argentina, Brazil, Colombia, and Mexico.

Clinical and Prognostic Factors Associated With Survival in Mexican Patients With Idiopathic Inflammatory Myopathies.

BACKGROUND: Factors associated with survival in patients with idiopathic inflammatory myopathies are heterogeneous. OBJECTIVE: This study aimed to describe clinical and prognostic factors associated with survival in Mexican patients with idiopathic inflammatory myopathies. METHODS: Patients with dermatomyositis (DM) and polymyositis (PM) seen at a tertiary care center from 1985 to 2012 were included. Demographic and clinical characteristics, comorbidities, treatment, and the time to death were recorded. Patients with juvenile DM were excluded. Univariate and multivariate analyses were performed to identify factors associated with mortality. RESULTS: A total of 264 patients with DM and 69 patients with PM were studied. Patients with DM had lower levels of creatine phosphokinase, less cumulative dose of prednisone, higher frequency of dysphagia, and no difference in frequency of interstitial lung disease compared with patients with PM. Patients with DM had lower survival during the first 4 years of disease (80%; 95% confidence interval [CI], 0.74-0.85 vs 89%; 95% CI, 0.78-0.95; P = 0.03 log-rank). Respiratory failure due to pulmonary infection was the main cause of death in patients with DM; miscellaneous causes were responsible for death in patients with PM. Muscular strength (hazard ratio [HR], 0.48; 95% CI, 0.27-0.83; P = 0.01), platelet count (HR, 0.98; 95% CI, 0.98-0.99; P = 0.002), as well as ever use of methotrexate (HR, 0.21; 95% CI, 0.07-0.65; P = 0.007) and azathioprine (HR, 0.21; 95% CI, 0.06-0.68; P = 0.009) were independent factors associated with mortality in patients with DM; in those with PM, only cancer was associated (HR, 8.0; 95% CI, 1.4-43.9; P = 0.01). CONCLUSIONS: Patients with DM had lower survival during the first 4 years of disease than patients with PM. Factors associated with mortality differed in both groups.

[Biologic therapies in the systemic vasculitides]. / Terapia biológica en las vasculitis sistémicas.

Several biological therapies have been evaluated in systemic vasculitis. Anti TNF-α agents may have a role in the treatment of Takayasu's arteritis and probably in giant cell arteritis. In Kawasaki's disease, infliximab is an option in subjects with intravenous immunoglobulin-resistant disease. Anti TNF-α cannot be recommended to treat ANCA-associated vasculitis. Anti-T lymphocyte globulin and alemtuzumab could have a role in the treatment of ANCA associated vasculitis, although current information about these two biological treatments comes from conventional resistant treatment cases, so the high incidence of complications and relapses observed with these treatment may be intrinsic to the severity of the disease and not related to the biological agents.

Current smoking status is associated to a non-ACR 50 response in early rheumatoid arthritis. A cohort study.

The purpose of this study is to determine factors associated with a non-ACR 50 response at 6 months of follow-up, in a cohort of patients with early rheumatoid arthritis (RA). Early RA patients (symptom duration <1 year), treated with the same combination treatment (methotrexate and sulfasalazine), were included. Demographic characteristics of the patients including current smoker status (defined as a patient that smokes at least one cigarette per day), years of formal education, a 28-joint count for swelling and tenderness were registered. A basal HAQ questionnaire, visual scales for global assessment, and pain were answered by all patients, and a CDAI basal score was calculated. The ACR 50 response was determined at 6 months follow-up. Multivariable logistic regression analysis was used to calculate adjusted ORs. Two hundred twenty-five patients were evaluated, but only 144 had a complete follow-up, 43% of the latter did not reach an ACR 50 response. The only factor associated with this outcome was current smoking (OR 3.58, P < 0.008, 95% CI 1.23-11.22). Low level of formal education (≤6 years) had a tendency towards a statistical difference (P < 0.08). After controlling with low level of formal education, sex, age in years, and CDAI baseline value with multivariable logistic regression analysis, current smoking status had an adjusted OR of 3.91 (P < 0.009, 95% CI 1.41-10.81). Smoking is associated with a non-ACR 50 response in early rheumatoid arthritis in patients treated with a combination therapy with methotrexate and sulfasalazine.

Morphologic diversity of chronic pigeon breeder's disease: clinical features and survival.

Morphology in chronic HP is characterized by bronchiolocentric mononuclear inflammation, poorly formed granulomas and variable degree of fibrosis. However, recent findings suggest that this disease may present different pathologic patterns. In this study we evaluated the clinical behavior and survival of patients with pigeon breeder's disease according to the pathologic pattern. One-hundred ten biopsies were classified as "typical" (n = 58), non-specific interstitial pneumonia (NSIP)-pattern (n = 22), usual interstitial pneumonia (UIP)-like (n = 10), mixed pattern (n = 9), organizing pneumonia (OP)-pattern (n = 3), airway-centered interstitial fibrosis (ACIF)-pattern (n = 3), and non-classified (n = 5). Clinical features and survival were compared between patients with "typical", NSIP, and UIP patterns. There were no statistical differences between the groups in age, gender, time of symptoms, smoking, clubbing, and PaO(2). By the one-way ANOVA test we found differences in the percent of lymphocytes in bronchoalveolar lavage (BAL; p < 0.002) and in the forced vital capacity (p < 0.05) between the 3 groups. After Bonferroni correction the difference in BAL lymphocytes remained significant among the UIP-like and the typical pattern (36.1 ± 22.9 versus 64.6 ± 20.9, p = 0.001). UIP-like patients exhibited the worst survival rate (HR: 4.19; 95% CI: 1.66-14.47; p < 0.004) while NSIP-like pattern showed the best survival (HR: 0.18; 95% CI: 0.04-0.82; p < 0.03). Multivariate Cox regression analysis revealed that patients with a UIP-like pattern retained a significantly worse survival (HR: 3.4 (IC 95%: 1.15-10.29; p < 0.03), and mortality for the NSIP group was best and approached statistical significance (p = 0.07). These findings demonstrate that a variety of histopathologic and imaging patterns are seen in PBD, and the presence of a UIP-like pattern confers the worst prognosis.

Idiopathic pulmonary fibrosis and emphysema: decreased survival associated with severe pulmonary arterial hypertension.

BACKGROUND: It has been suggested that the presence of emphysema modifies the outcome of patients with idiopathic pulmonary fibrosis (IPF). In this article we compare clinical features, smoking history, pulmonary function, estimated systolic pulmonary artery pressure (eSPAP), and mortality in IPF with emphysema vs IPF without emphysematous changes. METHODS: A cohort of 110 IPF patients was evaluated. Clinical data were collected from clinical charts. High-resolution CT (HRCT) scans were examined by an expert blinded to clinical data, and patients were classified into the following two groups: patients with IPF with emphysema; and patients with IPF without emphysema. The Kaplan-Meier method, log-rank test, and Cox regression model were used for statistical analyses. RESULTS: The prevalence of emphysema in the IPF cohort was 28% (31 of 110 patients). IPF with emphysema was significantly associated with male gender (odds ratio [OR], 18; 95% confidence interval [CI], 2.7 to 773.7; p = 0.0003), and smoking (OR, 3.8; 95% CI, 1.36 to 11.6; p = 0.004). Patients with IPF and emphysema had a higher mean (+/- SD) decrease in oxygen saturation during rest and exercise (16.3 +/- 6.7% vs 13.5 +/- 4.6%, respectively; p = 0.04), a higher mean fibrosis HRCT scan score (1.75 +/- 0.36 vs 1.55 +/- 0.38, respectively; p = 0.015), a higher eSPAP (82 +/- 20 vs 57 +/- 15 mm Hg, respectively; p < 0.0001), and lower median survival time (25 vs 34 months, respectively; p = 0.01) than patients with IPF without emphysema. The Cox regression model showed that the two most important variables associated with mortality were FVC < 50% predicted (hazard ratio [HR], 2.6; 95% CI, 1.19 to 5.68; p = 0.016) and eSPAP >or= 75 mm Hg (HR, 2.25; 95% CI, 1.12 to 4.54; p = 0.022). CONCLUSIONS: IPF patients with emphysema exhibited higher mortality compared with those with IPF without emphysema. This dire prognosis seems to be at least partially associated with the development of severe pulmonary arterial hypertension.