Prognostic Significance of Obstructive Sleep Apnea in a Population of Subjects with Interstitial Lung Diseases.

INTRODUCTION: Obstructive sleep apnea (OSA) is often observed in subjects with interstitial lung disease (ILD). It may have a negative impact on the course of ILD, but its prognostic significance in relation to other known indicators of poor outcome is unclear. METHODS: After a detailed work-up, including overnight unattended type III polygraphy, all subjects newly diagnosed with ILDs referred to our clinics were followed-up for at least 1.5 years or until death or progression of disease [> 10% decline in forced vital capacity (FVC) below baseline]. We analyzed relationships between some prespecified variables of interest, including sleeping results, to establish parameters predictive of progressive course. RESULTS: Our population consisted of 46 subjects (mean age 59.6 years; males 61%); 23.9% and 41% had idiopathic pulmonary fibrosis and ILD associated with systemic diseases, respectively. Mean baseline forced vital capacity and diffusion capacity of carbon monoxide were 83% and 57% of predicted, respectively. Mean (± SE) Apnea-Hypopnea Index (AHI) was 17 (± 3) events/h. AHI in the ranges 5-14.9, 15-29.9, and ≥ 30 was recorded in 14 (31%), 6 (13%), and 9 (20%) subjects, respectively. Mean distance covered in the 6-MWG walk test (6MWT) was 302 (± 19) m and 26 subjects (57%) showed exertional oxyhemoglobin desaturation. The median follow-up was about 18 months. Multivariate logistic regression analysis showed that exertional desaturation (HR 8.2; 1.8-36.5 95% CI; p = 0.006) and AHI ≥ 30, namely the threshold of severe OSA (HR 7.5; 1.8-30.6; p = 0.005), were the only independent variables related to progressive disease course. CONCLUSION: We conclude that exertional desaturation and elevated AHI had independent negative prognostic significance in our ILD population.

Network analysis studies in patients with eating disorders: A systematic review and methodological quality assessment.

INTRODUCTION: Network psychometrics has been enthusiastically embraced by researchers studying eating disorders (ED), but a rigorous evaluation of the methodological quality of works is still missing. This systematic review aims to assess the methodological quality of cross-sectional network analysis (NA) studies conducted on ED clinical populations. METHODS: PRISMA and PICOS criteria were used to retrieve NA studies on ED. Methodological quality was evaluated based on five criteria: variable-selection procedure, network estimation method, stability checks, topological overlap checks, and handling of missing data. RESULTS: Thirty-three cross-sectional NA studies were included. Most studies focused on populations that were female, white and, with an anorexia nervosa (AN) diagnosis. Depending on how many criteria were satisfied, 27.3% of studies (n = 9) were strictly adherent, 30.3% (n = 10) moderately adherent, 33.3% (n = 11) sufficiently adherent, and 9.1% (n = 3) poorly adherent. Missing topological overlap checks and not reporting missing data represented most unreported criteria, lacking, respectively, in 63.6% and 48.5% of studies. CONCLUSIONS: Almost all reviewed cross-sectional NA studies on ED report those methodological procedures (variable-selection procedure, network estimation method, stability checks) necessary for a network study to provide reliable results. Nonetheless these minimum reporting data require further improvement. Moreover, elements closely related to the validity of an NA study (controls for topological overlap and management of missing data) are lacking in most studies. Recommendations to overcome such methodological weaknesses in future NA studies on ED are discussed together with the need to conduct NA studies with longitudinal design, to address diversity issues in study samples and heterogeneity of assessment tools. PUBLIC SIGNIFICANCE: The present work aims to evaluate the quality of ED NA studies to support applications of this approach in ED research. Results show that most studies adopted basic procedures to produce reliable results; however, other important procedures linked to NA study validity were mostly neglected. Network methodology in ED is extremely promising, but future studies should consistently include topological overlap control procedures and provide information on missing data.

INTRODUCCIÓN: La psicometría de red ha sido aceptada con entusiasmo por los investigadores que estudian los trastornos de la conducta alimentaria (TCA), pero aún falta una evaluación rigurosa de la calidad metodológica de los trabajos. Esta revisión sistemática tiene como objetivo evaluar la calidad metodológica de los estudios de análisis de redes transversales (NA) realizados en poblaciones clínicas de TCA. MÉTODOS: Se utilizaron los criterios PRISMA y PICOS para recuperar los estudios de NA en TCA. La calidad metodológica se evaluó con base en 5 criterios: procedimiento de selección de variables, método de estimación de red, comprobaciones de estabilidad, comprobaciones de superposición topológica, manejo de datos faltantes. RESULTADOS: Se incluyeron 33 estudios transversales de NA. La mayoría de los estudios se centraron en poblaciones que eran mujeres, blancas y con un diagnóstico de anorexia nerviosa (AN). Dependiendo de cuántos criterios se cumplieron, el 27,3% de los estudios (n = 9) fueron estrictamente adherentes, el 30,3% (n = 10) moderadamente adherentes, el 33,3% (n = 11) suficientemente adherentes, el 9,1% (n = 3) poco adherentes. La falta de controles topológicos de superposición y el no reportar los datos faltantes representó la mayoría de los criterios no reportados, faltando respectivamente en el 63,6% y el 48,5% de los estudios. CONCLUSIONES: Casi todos los estudios transversales revisados de NA sobre TCA reportaron aquellos procedimientos metodológicos (procedimiento de selección de variables, método de estimación de red, comprobaciones de estabilidad) necesarios para que un estudio de red proporcione resultados confiables. No obstante, estos datos mínimos de presentación de reportes requieren mejoras adicionales. Además, en la mayoría de los estudios faltan elementos estrechamente relacionados con la validez de un estudio de NA (controles para la superposición topológica y el manejo de los datos faltantes). Las recomendaciones para superar tales debilidades metodológicas en futuros estudios de NA sobre los TCA son discutidos junto con la necesidad de realizar estudios de NA con diseño longitudinal, para abordar los problemas de diversidad en las muestras de estudio y la heterogeneidad de las herramientas de evaluación.

Peripheral and alveolar biomarkers of fibrotic hypersensitivity pneumonitis.

Fibrotic hypersensitivity pneumonitis (fHP) is a frequently misdiagnosed fibrosing interstitial pneumonia, which often remains undiagnosed due to the lack of uniformity of diagnostic criteria. Its features are similar to those of other ILDs, especially idiopathic pulmonary fibrosis (IPF), and biomarkers with potential clinical value have been proposed. We reviewed the recent literature on serum and BAL biomarkers, focusing on their clinical role in the diagnosis and management of fHP. We searched Medline/Pubmed results from 2005 until April 2020. The manuscripts of interest selected by our search were limited in number and proposed different clinical biomarkers in serum (IgG antibodies, macrophage inflammatory proteins-1, epithelial cell proteins) and BAL (lymphocytes, T-cell mediators). This is the first review to summarize all the serum and BAL biomarkers for fHP proposed in the literature. This review summarized the main biomarkers investigated in fibrotic hypersensitivity pneumonitis because an urgent aim of subsequent research will be to validate and standardize them for diagnostic purposes.

Adaptive immune system in pulmonary sarcoidosis-Comparison of peripheral and alveolar biomarkers.

Sarcoidosis is a multi-systemic granulomatous disease of unknown origin. Recent research has focused upon the role of autoimmunity in its development and progression. This study aimed to determine and define the disturbance and distribution of T and B cell subsets in the alveolar and peripheral compartments. Thirteen patients were selected for the study [median age, interquartile range (IQR) = 57 years (48-59); 23% were male]. Twelve healthy controls [median age, IQR = 53 years (52-65); 16% male] were also enrolled into the study. Cellular and cytokine patterns were measured using the cytofluorimetric approach. Peripheral CD8 percentages were higher in sarcoidosis patients (SP) than healthy controls (HC) (p = 0.0293), while CD4 percentages were lower (p = 0.0305). SP showed low bronchoalveolar lavage (BAL) percentages of CD19 (p = 0.0004) and CD8 (p = 0.0035), while CD19+ CD5+ CD27- percentages were higher (p = 0.0213); the same was found for CD4 (p = 0.0396), follicular regulatory T cells (Treg ) (p = 0.0078) and Treg (p < 0.0001) cells. Low T helper type 17 (Th17) percentages were observed in BAL (p = 0.0063) of SP. Peripheral CD4+ C-X-C chemokine receptor (CXCR)5+ CD45RA- ) percentages and follicular T helper cells (Tfh)-like Th1 (Tfh1) percentages (p = 0.0493 and p = 0.0305, respectively) were higher in the SP than HC. Tfh1 percentages and Tfh-like Th2 percentages were lower in BAL than in peripheral blood (p = 0.0370 and p = 0.0078, respectively), while CD4+ C-X-C motif CXCR5+ CD45RA- percentages were higher (p = 0.0011). This is the first study, to our knowledge, to demonstrate a link between an imbalance in circulating and alveolar Tfh cells, especially CCR4-, CXCR3- and CXCR5-expressing Tfh subsets in the development of sarcoidosis. These findings raise questions about the pathogenesis of sarcoidosis and may provide new directions for future clinical studies and treatment strategies.

Serum Concentrations of KL-6 in Patients with IPF and Lung Cancer and Serial Measurements of KL-6 in IPF Patients Treated with Antifibrotic Therapy.

BACKGROUND: Krebs von den Lungen-6 (KL-6) was suggested as ILD biomarker including idiopathic pulmonary fibrosis (IPF). Lung cancer is one of the most severe comorbidity of IPF patients. This study aims to serially analyze KL-6 in IPF patients after 24 months of Nintedanib and to first investigate the biomarker behavior in IPF associated with adenocarcinoma. MATERIALS AND METHODS: One hundred and forty-two ILD patients (median (IQR), 69 (63-75) years; 86 males) were retrospectively enrolled. Serial serum samples were collected from IPF patients before starting antifibrotic therapy and after 12 months. Serum KL-6 levels were measured by KL-6 reagent assay (Fujirebio Europe, UK). RESULTS: Increased KL-6 concentrations were identified in IPF-LC patients than IPF, fibrotic hypersensitivity pneumonitis, and pulmonary fibrosis associated with autoimmune disease groups. A cut-off value was calculated to distinguish IPF and IPF-LC patients. IPF patients monitored for 24 months with Nintedanib showed persisted increased levels of KL-6 with a progressive decline of FVC percentages. CONCLUSION: This preliminary study offers a first demonstration that very high serum concentrations of KL-6 in IPF-LC patients are associated with poor prognosis. Moreover, serial evaluation of serum KL-6 in IPF patients over 24 months of Nintedanib treatment revealed that most patients experienced a stabilization of lung function parameters and of serum concentrations of KL-6.

Systematic Review and Metanalysis of Oncomarkers in IPF Patients and Serial Changes of Oncomarkers in a Prospective Italian Real-Life Case Series.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a severe progressive interstitial lung disease. At 5-year follow-up, 15% of IPF patients develop lung cancer, which significantly reduces the survival rate. Here we review the literature on the clinical role of oncomarkers in IPF progression, and describe the trend of routine oncomarkers in IPF patients over the longest follow-up yet reported. MATERIALS AND METHODS: A systematic search of the literature in PubMed was performed to find relevant studies published up to 24 September 2020. The most common oncomarkers were chosen to select papers related to pulmonary fibrosis. Then, 24 IPF patients and 25 non-IPF patients, followed at Careggi ILD Referral Centre and Siena Regional Referral Centre for ILD, were enrolled consecutively. RESULTS: A few studies reported an association between serum oncomarkers and severity of IPF. NSE, CEA, Ca19.9, and Ca125 were higher in the IPF, than in the non-IPF, group at every follow-up (p < 0.05). Ca15.3 concentrations were higher in the IPF, than the non-IPF, group at t3 (p = 0.0080) and t4 (p = 0.0168). To improve the specificity and sensitivity of Ca15.3, a panel of biomarkers was analyzed, with the IPF group as dependent variable, and chitotriosidase, Cyfra 21.1, Ca15.3, Ca125, and Ca19.9 as independent variables. CONCLUSIONS: This study focused on the discovery of multiple biomarker signatures, such as combinations of oncomarkers, that are widely and routinely available in biochemistry laboratories. The combination of clinical parameters and biological markers could help achieve more accurate results regarding prognosis and response to treatment in IPF. Our results could pave the way for a more "personalized" medical approach to patients affected by IPF.

Antithrombin III as predictive indicator of survival in idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib: a preliminary study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease often managed with nintedanib, a tyrosine kinase inhibitor targeting several profibrotic pathways. Although clotting processes are involved in wound healing and repair in the lung, there are no data on the role of antithrombin III (ATIII) in IPF patients treated with nintedanib. A previous proteomic analysis of serum of IPF patients before and after 1 year of nintedanib treatment showed differential protein expression of ATIII. AIMS: Here we used quantitative methods to evaluate differential ATIII concentrations in IPF patients before and after 1 year of nintedanib treatment and to assess the potential of ATIII as a prognostic biomarker in IPF patients. METHODS: Serum levels of ATIII were measured by enzyme-linked immunosorbent assay in 14 IPF patients before and after 1 year of nintedanib treatment. RESULTS: A statistically significant inverse correlation was found between serum ATIII concentrations and pulmonary function test parameters in all patients at baseline and follow up. Baseline serum ATIII and bronchoalveolar lavage (BAL) neutrophils proved to be reliable predictors of poor prognosis. A baseline ATIII threshold of 126.5 µg/mL discriminated survivors from non-survivors. CONCLUSIONS: After 12 months of antifibrotic treatment, IPF patients with high serum ATIII concentrations and high BAL neutrophil percentages had a poor prognosis and increased survival risk. The results of this preliminary study suggest that ATIII has potential as a biomarker of IPF severity and in predicting response to nintedanib therapy. As a marker, ATIII showed several advantages over BAL neutrophil percentage.

Coronavirus HKU 1 infection with bronchiolitis, pericardial effusion and acute respiratory failure in obese adult female.

Seven species of coronavirus cause acute respiratory illness in humans. Coronavirus HKU 1 (CoV HKU 1) was first described in 2005 in an adult patient with pneumonia in Hong Kong. Although it is a well-known respiratory tract pathogen, there is not much information about its role in hospitalized adults, especially in southern Europe. Here, we describe a case of radiologically demonstrated CoV HKU 1-related bronchiolitis with acute respiratory failure in an adult female without significant comorbidities except obesity.

Extended Exhaled Nitric Oxide Analysis in Interstitial Lung Diseases: A Systematic Review.

Fractional exhaled nitric oxide (FeNO) is a well-known and widely accepted biomarker of airways inflammation that can be useful in the therapeutic management, and adherence to inhalation therapy control, in asthmatic patients. However, the multiple-flows assessment of FeNO can provide a reliable measurement of bronchial and alveolar production of NO, supporting its potential value as biomarker also in peripheral lung diseases, such as interstitial lung diseases (ILD). In this review, we first discuss the role of NO in the pathobiology of lung fibrosis and the technique currently approved for the measurement of maximum bronchial flux of NO (J'awNO) and alveolar concentration of NO (CaNO). We systematically report the published evidence regarding extended FeNO analysis in the management of patients with different ILDs, focusing on its potential role in differential diagnosis, prognostic evaluation and severity assessment of disease. The few available data concerning extended FeNO analysis, and the most common comorbidities of ILD, are explored too. In conclusion, multiple-flows FeNO analysis, and CaNO in particular, appears to be a promising tool to be implemented in the diagnostic and prognostic pathways of patients affected with ILDs.

Krebs von den Lungen-6 as a biomarker for disease severity assessment in interstitial lung disease: a comprehensive review.

Aim: Interstitial lung diseases (ILD) are a group of lung disorders characterized by interstitial lung thickening. Krebs von den Lungen-6 (KL-6) is a molecule that is predominantly expressed by damaged alveolar type II cells and it has been proposed as a potential biomarker of different ILD. Materials & methods: A growing literature about KL-6 has been reviewed and selected to evaluate its role in the clinical management of ILD to predict disease diagnosis, activity, prognosis and treatment response. Results: KL-6 concentrations have been evaluated in fibrotic and granulomatous lung diseases and it was demonstrated to be a biomarker of disease severity useful for clinical follow-up of ILD patients. KL-6 levels differentiated between fibrotic ILD, such as idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis, and nonfibrotic lung disorders, including sarcoidosis and pulmonary alveolar proteinosis. Conclusion: KL-6 is predictive biomarker useful in the clinical management of ILD patients, in particular in patients with severe fibrotic lung disorders.

The Role of Urinary Calcium and Chitotriosidase in a Cohort of Chronic Sarcoidosis Patients.

BACKGROUND: Calcium metabolism alterations are quite common in sarcoidosis and have been correlated with disease activity. OBJECTIVES: The aim of the study was to investigate the clinical significance of calcium metabolism alterations in patients with chronic sarcoidosis. We paid particular attention to associations with specific disease phenotypes and chitotriosidase (CTO) expression. METHODS: 212 chronic sarcoidosis patients (mean age 56.07 ± 12 years; 97 males) were retrospectively recruited. Demographic, clinical, functional, and radiological data, and serum-urinary calcium metabolism were entered into an electronical database for analysis. Levels of CTO and angiotensin-converting enzyme (ACE) were measured and bone mineral density and lung function tests were conducted. RESULTS: Hypercalciuria and hypercalcemia were observed in 18.8 and 1.8% of patients, respectively. Urinary calcium levels correlated with CTO activity (r = 0.33, p = 0.0042). Patients with worsening persistent disease showed the highest levels of urinary calcium. Diffusing capacity of the lung for carbon monoxide (DLCO) percentage correlated inversely with urinary calcium (r = 0.1482; p = 0.0397). CONCLUSIONS: Calcium metabolism alteration, particularly hypercalciuria, was observed in a significant percentage of patients of sarcoidosis. Urinary calcium was correlated with clinical status, DLCO, and serum CTO activity, suggesting its potential role as a biomarker of the activity and severity of sarcoidosis.

Bronchoalveolar lavage and serum KL-6 concentrations in chronic hypersensitivity pneumonitis: correlations with radiological and immunological features.

Chronic hypersensitivity pneumonitis (cHP) is a fibrotic interstitial lung disease (ILD) resulting from inhalation of different organic substances and chemical compounds determining an inflammatory and immunological response in sensitized individuals. KL-6, a human mucin protein expressed by type 2 pneumocytes, has been proposed as a prognostic biomarker of cHP. Assessment of usefulness KL-6 in ILD has been investigated primarily in Asiatic population. The aim of this study was to evaluate clinical utility of KL-6 in serum and bronchoalveolar lavage (BAL). In this study, we retrospectively analysed clinical, radiological and immunological data of a cohort of 42 patients affected by cHP: KL-6 concentrations were collected from serum and BAL. KL-6 clinical value was assessed through the analysis of association between KL-6 concentrations and clinical, functional, immunological and radiological features. KL-6 serum concentration results increased in 28/34 patients (82%). A positive direct correlation was observed between KL-6 concentrations in BAL and serum (r = 0.62, p < 0.05). In our study population we found that patients with extensive presence of ground glass opacities and centrilobular nodules at high-resolution computed tomography (HRCT) showed the highest concentrations of KL-6 in BAL and a predominantly CD3+ CD8+ BAL lymphocytosis. BAL lymphocytosis and KL-6 concentrations showed a direct correlation. BAL KL-6, a result of alveolar damage, caused in cHP by CD3+ CD8+ mediated flogosis and suggested by radiological evidence of ground-glass opacities and centrilobular nodules, can be considered a useful biomarker to assess, along with BAL cellular analysis and HRCT findings, disease activity.

Pirfenidone in idiopathic pulmonary fibrosis: real-life experience in the referral centre of Siena.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and has a median survival after diagnosis of 2-5 years. Pirfenidone is the first approved antifibrotic drug for the treatment of IPF. Here we report the functional progress, side effects and survival data of a population of patients with IPF, diagnosed at our centre and treated with pirfenidone. METHODS: We enrolled 91 patients with IPF (71 males) treated with pirfenidone. Clinical, survival and functional details were collected retrospectively at start of therapy and after 12, 24, 36 and 48 months of treatment. Lung function tests at least 12 months before starting therapy were available for 40 patients and were entered in the database, as well as side effects. RESULTS: During the observation period (922 ± 529 days), 27 patients died, 5 patients underwent lung transplant and 10 patients interrupted therapy due to adverse events or IPF progression. The median survival was 1606 days. There was a significant reduction in disease progression rate, as measured by trend of forced vital capacity, after 1 year of therapy with respect to before treatment (p = 0.0085). Forced vital capacity reduction rate was progressively higher in the subsequent years of treatment. Treatment-related side effects were reported in 25 patients and were predominantly mild. Overall, four patients discontinued therapy due to severe photosensitivity. CONCLUSIONS: Our findings confirm the efficacy of pirfenidone in reducing functional progression of IPF and its excellent safety profile in a real-life setting. This study, designed on a long-term follow up, contributes to the growing evidence on safety, tolerability and efficacy of pirfenidone in IPF. The reviews of this paper are available via the supplemental material section.

Alveolar nitric oxide is related to periostin levels in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive diffuse lung disease leading to chronic respiratory failure and death in 3-5 years. Among potential prognostic biomarkers, alveolar nitric oxide (CaNO) and serum periostin showed to predict mortality and disease progression in these patients. The aim of this study is to investigate potential correlations between CaNO and serum periostin and evaluate their prognostic value. METHODS: Fifty-nine patients with IPF (47 males, 65.5±9.5 years old) were recruited in Siena Regional Referral Center for Interstitial Lung Disease. In this population, we retrospectively collected multiple-flows exhaled nitric oxide parameters and serum periostin at diagnosis and compared these values with a control group of 60 and 8 healthy volunteers, respectively. Clinical, functional and survival data were collected according to our Center follow-up program. RESULTS: IPF patients reported higher levels of CaNO but not of periostin in respect with healthy controls (P<0.0001 and P=0.1096, respectively). CaNO significantly correlated with periostin levels and TLCO% (P<0.0001 and P=0.0205, respectively). Patients with CaNO>6 ppb showed a worse prognosis, close to statistical significance (P=0.0628). No difference in survival time was found according to periostin levels. CONCLUSIONS: CaNO was significantly higher in IPF patients and was related to functional severity of disease. CaNO levels correlated with periostin, suggesting a potential common pathway between the biomarkers.

Alveolar concentration of nitric oxide as a prognostic biomarker in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease leading to respiratory failure and death in 2-5 years from diagnosis. To date, clinical course of disease and prognosis cannot be predicted with an acceptable accuracy. Recently, alveolar concentration of nitric oxide (CaNO) has been proposed as a marker of severity of IPF, but its prognostic value in this setting is unknown. AIM OF THE STUDY: To evaluate the reliability of CaNO as a prognostic biomarker in patients with IPF. METHODS: In the Siena Referral Centre for Interstitial Lung Diseases, multiple-flows exhaled nitric oxide analysis was performed to measure CaNO in a cohort of 88 patients with IPF and in 60 healthy controls. In this population, we evaluate functional disease progression and survival according to the follow-up of our Centre. Clinical, functional and radiological data were collected at baseline to investigate correlations with CaNO levels. RESULTS: IPF patients showed significantly higher levels of CaNO than healthy controls (p < 0.0001); CaNO was significantly correlated with many pulmonary functional parameters. Survival analysis showed that all patients with CaNO ≥6 ppb reported a significantly worse outcome. Disease progression, expressed as FVC time to decline to 10% (TTD10), occurred significantly earlier in patients with CaNO ≥ 9 ppb. CONCLUSION: We confirm that CaNO was significantly higher in IPF patients than in healthy controls and its correlation with functional parameters. Moreover, CaNO ≥6 and ≥9 ppb were significantly correlated with mortality and disease progression, respectively. These data suggest that CaNO, a non-invasive and reproducible biomarker, may predict disease progression and survival outcome in patients with IPF.

Pirfenidone Therapy for Familial Pulmonary Fibrosis: A Real-Life Study.

INTRODUCTION: Familial pulmonary fibrosis (FPF) is defined as an idiopathic diffuse parenchymal lung disease affecting two or more members of the same primary biological family. The aim of this study was to compare disease progression and tolerance to pirfenidone in a population of FPF patients who presented with radiological and/or histological evidence of UIP, and a group of idiopathic pulmonary fibrosis (IPF) patients. METHODS: Seventy-three patients (19 with FPF and 54 with IPF) were enrolled and data were collected retrospectively at 6, 12 and 24 months follow-up. RESULTS: FPF patients were statistically younger and more frequently females. A significantly greater decline in FVC and DLCO was recorded in FPF than in IPF patients at 24 months follow-up. At the 6-min walking test, walked distance declined significantly in FPF patients than IPF at 24 months. No statistically significant differences in drug tolerance or side effects were recorded between groups. CONCLUSION: Different rate of progression was observed in patients with IPF and FPF on therapy with pirfenidone; our findings may not be due to lack of effectiveness of therapy, but to the different natural history and evolution of these two conditions. Pirfenidone was well tolerated by FPF and IPF patients. Specific unbiased randomized clinical trials on larger populations to validate our preliminary exploratory results are needed.

Evaluation of multiple-flows exhaled nitric oxide in idiopathic and non-idiopathic interstitial lung disease.

BACKGROUND: fractional exhaled nitric oxide (FeNO) is a non-invasive and reproducible marker of nitrosative stress and lung inflammation. More recently, FeNO has been proposed as a marker of severity of idiopathic pulmonary fibrosis (IPF) and systemic sclerosis associated ILD. AIM AND OBJECTIVES: to evaluate the role of FeNO in the diagnostic pathway of ILDs. METHODS: according to ERS guidelines for exhaled biomarkers in lung diseases, FeNO at multiple flow-rates (50-100-150 and 350 ml s-1) and alveolar concentration of NO (CaNO) were collected in 60 healthy controls and 134 patients affected by ILD: 50 with IPF, 19 with fibrotic non-specific interstitial pneumonia, 19 with chronic hypersensitivitis pneumonia (cHP) and 46 with connective tissue disease related ILD (CTD-ILD). ROC curves were performed to investigate the potential role of eNO parameters in discriminating between idiopathic and non-idiopathic ILDs. RESULTS: all ILD groups reported higher levels of FeNO 150-350 ml s-1 and CaNO than controls. Among ILDs, CTD-ILD showed more elevated FeNO 350 ml s-1 and CaNO levels than other ILD. In particular, CaNO reported the best diagnostic accuracy to discriminate CTD-ILD from idiopathic ILDs. CONCLUSIONS: patients affected by ILD reported increased FeNO 150-350 ml s-1 and CaNO in respect with healthy controls, indicating a potential role of nitrosative stress in lung fibrosis. The significant difference of CaNO levels between idiopathic ILDs and CTD-ILD is interesting and may suggest that NO is also implicated in lung inflammation associated with rheumatological disease. Further evidence is necessary to establish if CaNO is worthy of attention in the differential diagnosis of ILDs.

Caracterización de la red vincular de la población adolescente que presenta conducta suicida / Characterization of the bonding network of the adolescent population that presents suicidal behavior

INTRODUCCIÓN El suicidio es un problema multicausal que tiene un gran impacto social, económico, familiar y psicológico a nivel mundial. Según la OMS, el suicidio es la segunda causa de muerte en jóvenes de 15 a 29 años. Desde la Dirección de Estadísticas e Información de Salud de Argentina se informó que de 2007 a 2014 el mayor número de suicidios se registran en ambos sexos entre los 15 y 24 años. A nivel local, en Bahía Blanca el número de intentos de suicidio en el rango etario de 11 a 19 años ha ido en aumento en los últimos tres años. OBJETIVO Describir las características de la red vincular de la población adolescente de 13 a 18 años que ingresa por Conducta Suicida a los Servicios Municipales de Urgencia (SMU) de Bahía Blanca. MÉTODOS Se realizó un estudio observacional, exploratorio de corte transversal, de índole cuali-cuantitativo. En virtud de nuestro objetivo se puso particular atención a la dimensión relacional del evento y a la descripción que el adolescente realiza de sus vínculos sociales. Nuestra muestra se conformó de 30 adolescentes, habiendo prestado consentimiento para llevar a cabo una entrevista semiestructurada 14 adolescentes; 13 mujeres y 1 varón. El análisis cuantitativo del estudio se basa en la interpretación de las variables volcadas en una base de datos a través del programa SPSS versión 21. Con relación al aspecto cualitativo, se utilizó el Método de Análisis Fenomenológico Interpretativo. RESULTADOS Registramos que el 73% de la muestra son mujeres, pero que los hombres eligen los métodos más letales. Los conflictos con el mundo adulto aparecen como factores concurrentes del acto, mientras que el conflicto con pares lo precipitan. DISCUSIÓN La percepción que el adolescente tiene sobre su red vincular impacta en la decisión de la conducta suicida. A su vez, podemos conjeturar que el acto suicida entrama una dimensión relacional dirigida al otro de la red social