Ivette Buendía-Roldán

Familial pulmonary fibrosis is the strongest risk factor for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disorder of unknown etiology. The disease is likely the result of complex interactions between genetic and environmental factors. Evidence suggests that certain environmental factors, such as cigarette smoking and metal dust exposures, or comorbidities like gastroesophageal reflux, and type 2 diabetes mellitus (DM2) may increase risk to develop IPF. Substantial uncertainty remains, however, regarding these and other putative risk factors for IPF. In this study we performed a case-control analysis including 100 patients with IPF and 263 controls matched for age sex and place of residence. We used a structured questionnaire to identify potential risk factors for IPF, including environmental and occupational exposures as well as the relevance of family history of pulmonary fibrosis. The multivariate analysis revealed that family history of pulmonary fibrosis [OR = 6.1, CI95% 2.3-15.9; p < 0.0001] was strongly associated with increased risk of IPF. Actually, 20% of the cases reported a parent or sibling with pulmonary fibrosis. Gastroesophageal reflux [OR = 2.9, CI: 1.3-6.6; p = 0.007], former cigarette smoking [OR = 2.5, CI: 1.4-4.6, p = 0.003], and past or current occupational exposure to dusts, smokes, gases or chemicals [OR = 2.8, CI: 1.5-5.5; p = 0.002] were also associated with the disease. Despite being a significant risk factor on univariate analysis DM2 was not significant in multivariate analysis. These findings indicate that family history of pulmonary fibrosis is a strong risk factor for IPF. Also, we confirmed that occupational exposures, gastroesophageal reflux and former smoking increase the risk for this disease.

Fibrocytes contribute to inflammation and fibrosis in chronic hypersensitivity pneumonitis through paracrine effects.

RATIONALE Hypersensitivity pneumonitis (HP) represents a lung inflammation provoked by exposure to a variety of antigens. Chronic HP may evolve to lung fibrosis. Bone marrow-derived fibrocytes migrate to injured tissues and contribute to fibrogenesis, but their role in HP is unknown. OBJECTIVES To assess the possible participation of fibrocytes in chronic HP. METHODS CD45(+)/CXCR4(+)/Col-I(+) circulating fibrocytes were evaluated by flow cytometry, and the presence of fibrocytes in HP and normal lungs by confocal microscopy. The concentration of CXCL12 in plasma and bronchoalveolar lavage fluids was quantified by ELISA. The effect of fibrocytes on lung fibroblasts and T lymphocytes was examined in co-cultures. MEASUREMENTS AND MAIN RESULTS The percentage of circulating fibrocytes was significantly increased in patients with HP compared with healthy individuals (5.3 ± 3.4% vs. 0.8 ± 0.7%; P = 0.00004). Numerous fibrocytes were found infiltrating the HP lungs near fibroblasts and lymphocytes. Plasma CXCL12 concentration was significantly increased in patients with HP (2,303.3 ± 813.7 vs. 1,385.6 ± 318.5 pg/ml; P = 0.00003), and similar results were found in bronchoalveolar lavage fluids. The chemokine was primarily expressed by epithelial cells. In co-cultures, fibrocytes induced on lung fibroblasts a significant increase in the expression of α1 type I collagen, matrix metalloprotease-1, and platelet-derived growth factor-β. Likewise, fibrocytes induced the up-regulation of CCL2 in HP lymphocytes and fibroblasts. CONCLUSIONS These findings demonstrate that high levels of fibrocytes are present in the peripheral blood of patients with chronic HP and that these cells infiltrate the HP lungs. Fibrocytes may participate in the pathogenesis of HP, amplifying the inflammatory and fibrotic response by paracrine signaling inducing the secretion of a variety of proinflammatory and profibrotic molecules.

Hookah, is it really harmless?

The hookah is a snuff smoking device whose origin dates back to the fifteenth century, has been used extensively in the Middle East in recent decades has become popular in Western culture countries, particularly in Americas and Europe. It has been reported that like other forms smoking tobacco, their use can lead to addiction also is used for inhaling and other addictive substances. Has also been considered a risk factor for various isolated diseases, including chronic obstructive pulmonary disease (COPD), different types of cancer, hemodynamic alterations, vascular disease, infectious diseases, among others. In pregnant women has been reported that there use condition a diminution on fetal growth and different diseases in the newborn. It was also mentioned that hookah smoke contains several toxic substances that can affect both, the primary and the passive smoker, so we did this review to determine the complications associated with its use.

Increased Expression of CC16 in Patients with Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown etiology. The pathogenic mechanisms are unclear, but evidence indicates that aberrantly activated alveolar epithelial cells secrete a variety of mediators which induce the migration, proliferation and activation of fibroblasts and finally the excessive accumulation of extracellular matrix with the consequent destruction of the lung parenchyma. CC16 (approved symbol SCGB1A1), a putative anti-inflammatory protein produced by “club” cells in the distal airways, has not been evaluated in IPF lungs. In this study, we determined the serum and bronchoalveolar lavage (BAL) levels as well as the lung cell localization of this protein. Also, we explored the usefulness of serum levels of CC16 for the differential diagnosis of IPF (n = 85), compared with non-IPF interstitial lung diseases [chronic hypersensitivity pneumonitis (cHP; n = 85) and connective tissue diseases (CTD-ILD; n = 85)]. CC16 was significantly increased in serum and BAL fluids of IPF patients and was found not only in club cells but also in alveolar epithelial cells. When compared with non-IPF patients and controls, serum levels were significantly increased (p<0.0001). Sensitivity and specificity for CC16 (cut-off 41ng/mL) were 24% and 90%, positive predictive value 56% and negative predictive value 69%. These findings demonstrate that CC16 is upregulated in IPF patients suggesting that may participate in its pathogenesis. Although higher than the serum levels of non-IPF patients it shows modest sensitivity to be useful as a potential biomarker for the differential diagnosis.

Hemorragia alveolar difusa: causas y desenlaces en un instituto de tercer nivel

OBJECTIVE To identify the most common causes of diffuse alveolar hemorrhage (DAH) and the evolution of cases during hospitalization. PATIENTS AND METHODS A review of cases diagnosed with DAH; the diagnoses were classified according to existing criteria and the progression of the cases was determined. RESULTS We identified 17 cases of DAH, with the leading cause being ANCA associated vasculitis (41% of cases), followed by cases secondary to drugs (18%). In 35% of the cases, there was a failure in identifying an etiology. Six patients died (35%), the only factor associated with mortality was male gender 5/6 vs 3/11, p=0.05. CONCLUSIONS The most frequent cause of alveolar hemorrhage was ANCA associated vasculitis. The mortality in DAH is about 35%, males seem to have a worse prognosis.

Idiopathic pulmonary fibrosis: Clinical behavior and aging associated comorbidities

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible and usually lethal lung disease of unknown etiology. Once considered as a relatively homogeneous, slowly progressive disease, is now recognized that the clinical behavior shows substantial heterogeneity, including an accelerated variant, and the presence of acute exacerbations. In addition, since IPF largely affects individuals over 60 years of age, the patients are at increased risk of several comorbidities that in turn have a remarkable clinical impact on the disease and increases mortality rate. Among others, combined pulmonary fibrosis and emphysema, secondary pulmonary arterial hypertension, lung cancer, and cardiovascular diseases are frequently associated with IPF and impact survival. For these reasons clinical phenotypes and comorbidities should be timely identified and managed. The aim of this review is to describe the common pulmonary and extra-pulmonary comorbidities in IPF, as well as the putative mechanisms involved.

Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline

Background: This document provides clinical recommendations for the diagnosis of idiopathic pulmonary fibrosis (IPF). It represents a collaborative effort between the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. Methods: The evidence syntheses were discussed and recommendations formulated by a multidisciplinary committee of IPF experts. The evidence was appraised and recommendations were formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Results: The guideline panel updated the diagnostic criteria for IPF. Previously defined patterns of usual interstitial pneumonia (UIP) were refined to patterns of UIP, probable UIP, indeterminate, and alternate diagnosis. For patients with newly detected interstitial lung disease (ILD) who have a high‐resolution computed tomography scan pattern of probable UIP, indeterminate, or an alternative diagnosis, conditional recommendations were made for performing BAL and surgical lung biopsy; because of lack of evidence, no recommendation was made for or against performing transbronchial lung biopsy or lung cryobiopsy. In contrast, for patients with newly detected ILD who have a high‐resolution computed tomography scan pattern of UIP, strong recommendations were made against performing surgical lung biopsy, transbronchial lung biopsy, and lung cryobiopsy, and a conditional recommendation was made against performing BAL. Additional recommendations included a conditional recommendation for multidisciplinary discussion and a strong recommendation against measurement of serum biomarkers for the sole purpose of distinguishing IPF from other ILDs. Conclusions: The guideline panel provided recommendations related to the diagnosis of IPF.

Predictive factors and prognostic effect of telomere shortening in pulmonary fibrosis: Telomeric clinical implications in IPF

The abnormal shortening of telomeres is a mechanism linking ageing to idiopathic pulmonary fibrosis (IPF) that could be useful in the clinical setting. The objective of this study was to identify the IPF patients with higher risk for telomere shortening and to investigate the outcome implications.

Transmembrane protease, serine 4 (TMPRSS4) is upregulated in IPF lungs and increases the fibrotic response in bleomycin-induced lung injury

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease characterized by epithelial cell activation, expansion of the fibroblast population and excessive extracellular matrix accumulation. The mechanisms are incompletely understood but evidence indicates that the deregulation of several proteases contributes to its pathogenesis. Transmembrane protease serine 4 (TMPRSS4) is a novel type II transmembrane serine protease that may promote migration and facilitate epithelial to mesenchymal transition (EMT), two critical processes in the pathogenesis of IPF. Thus, we hypothesized that over-expression of TMPRSS4 in the lung could promote the initiation and/or progression of IPF. In this study we first evaluated the expression and localization of TMPRSS4 in IPF lungs by real time PCR, western blot and immunohistochemistry. Then we examined the lung fibrotic response in wild-type and TMPRSS4 deficient mice using the bleomycin-induced lung injury model. We found that this protease is upregulated in IPF lungs, where was primarily expressed by epithelial and mast cells. Paralleling the findings in vivo, TMPRSS4 was expressed by alveolar and bronchial epithelial cells in vitro and unexpectedly, provoked an increase of E-cadherin. No expression was observed in normal human or IPF lung fibroblasts. The lung fibrotic response evaluated at 28 days after bleomycin injury was markedly attenuated in the haplodeficient and deficient TMPRSS4 mice. By morphology, a significant reduction of the fibrotic index was observed in KO and heterozygous mice which was confirmed by measurement of collagen content (hydroxyproline: WT: 164±21.1 μg/lung versus TMPRSS4 haploinsufficient: 110.2±14.3 μg/lung and TMPRSS4 deficient mice: 114.1±24.2 μg/lung (p<0.01). As in IPF, TMPRSS4 was also expressed in epithelial and mast cells. These findings indicate that TMPRSS4 is upregulated in IPF lungs and that may have a profibrotic role.

Identification of MMP28 as a biomarker for the differential diagnosis of idiopathic pulmonary fibrosis

Background and objective Idiopathic Pulmonary Fibrosis (IPF) is a progressive disease of unknown etiology. The diagnosis is based on the identification of a pattern of usual interstitial pneumonia either by high resolution computed tomography and/or histology. However, a similar pattern can be observed in other fibrotic lung disorders, and precise diagnosis remains challenging. Studies on biomarkers contributing to the differential diagnosis are scanty, and still in an exploratory phase. Our aim was to evaluate matrix metalloproteinase (MMP)-28, which has been implicated in abnormal wound healing, as a biomarker for distinguishing IPF from fibrotic non-IPF patients. Methods The cell localization of MMP28 in lungs was examined by immunohistochemistry and its serum concentration was measured by ELISA in two different populations. The derivation cohort included 82 IPF and 69 fibrotic non-IPF patients. The validation cohort involved 42 IPF and 41 fibrotic non-IPF patients. Results MMP28 was detected mainly in IPF lungs and localized in epithelial cells. In both cohorts, serum concentrations of MMP28 were significantly higher in IPF versus non-IPF (mostly with lung fibrosis associated to autoimmune diseases and chronic hypersensitivity pneumonitis) and healthy controls (ANOVA, p<0.0001). The AUC of the derivation cohort was 0.718 (95%CI, 0.635–0.800). With a cutoff point of 4.5 ng/mL, OR was 5.32 (95%CI, 2.55–11.46), and sensitivity and specificity of 70.9% and 69% respectively. The AUC of the validation cohort was 0.690 (95%CI, 0.581–0.798), OR 4.57 (95%CI, 1.76–12.04), and sensitivity and specificity of 69.6% and 66.7%. Interestingly, we found that IPF patients with definite UIP pattern on HRCT showed higher serum concentrations of MMP28 than non-IPF patients with the same pattern (7.8±4.4 versus 4.9±4.4; p = 0.04). By contrast, no differences were observed when IPF with possible UIP-pattern were compared (4.7±3.2 versus 3.9±3.0; p = 0.43). Conclusion These findings indicate that MMP28 might be a useful biomarker to improve the diagnostic certainty of IPF.