A non-invasive continuous and real-time volumetric monitoring in spontaneous breathing subjects based on bioimpedance-ExSpiron®Xi: a validation study in healthy volunteers.

Tidal volume (TV) monitoring breath-by-breath is not available at bedside in non-intubated patients. However, TV monitoring may be useful to evaluate the work of breathing. A non-invasive device based on bioimpedance provides continuous and real-time volumetric tidal estimation during spontaneous breathing. We performed a prospective study in healthy volunteers aimed at evaluating the accuracy, the precision and the trending ability of measurements of ExSpiron®Xi as compared with the gold standard (i.e. spirometry). Further, we explored whether the differences between the 2 devices would be improved by the calibration of ExSpiron®Xi with a pre-determined tidal volume. Analysis accounted for the repeated nature of measurements within each subject. We enrolled 13 healthy volunteers, including 5 men and 8 women. Tidal volume, TV/ideal body weight (IBW) and respiratory rate (RR) measured with spirometer (TVSpirometer) and with ExSpiron®Xi (TVExSpiron) showed a robust correlation, while minute ventilation (MV) showed a weak correlation, in both non/calibrated and calibrated steps. The analysis of the agreement showed that non-calibrated TVExSpiron underestimated TVspirometer, while in the calibrated steps, TVExSpiron overestimated TVspirometer. The calibration procedure did not reduce the average absolute difference (error) between TVSpirometer and TVExSpiron. This happened similarly for TV/IBW and MV, while RR showed high accuracy and precision. The trending ability was excellent for TV, TV/IBW and RR. The concordance rate (CR) was >95% in both calibrated and non-calibrated measurements. The trending ability of minute ventilation was limited. Absolute error for both calibrated and not calibrated values of TV, TV/IBW and MV accounting for repeated measurements was variably associated with BMI, height and smoking status. Conclusions: Non-invasive TV, TV/IBW and RR estimation by ExSpiron®Xi was strongly correlated with tidal ventilation according to the gold standard spirometer technique. This data was not confirmed for MV. The calibration of the device did not improve its performance. Although the accuracy of ExSpiron®Xi was mild and the precision was limited for TV, TV/IBW and MV, the trending ability of the device was strong specifically for TV, TV/IBW and RR. This makes ExSpiron®Xi a non-invasive monitoring system that may detect real-time tidal volume ventilation changes and then suggest the need to better optimize the patient ventilatory support.

Hemodynamic failure and graft dysfunction after lung transplant: A possible clinical continuum with immediate and long-term consequences.

INTRODUCTION: The postoperative hemodynamic management after lung transplant (LUTX) is guided by limited evidence. We aimed to describe and evaluate risk factors and outcomes of postoperative vasoactive support of LUTX recipients. METHODS: In a single-center retrospective analysis of consecutive adult LUTX, two cohorts were identified: (1) patients needing prolonged vasoactive support (>12 h from ICU admission) (VASO+); (2) or not (VASO-). Postoperative hemodynamic characteristics were thoroughly analyzed. Risk factors and outcomes of VASO+ versus VASO- cohorts were assessed by multivariate logistic regression and propensity score matching. RESULTS: One hundred and thirty-eight patients were included (86 (62%) VASO+ versus 52 (38%) VASO-). Vasopressors (epinephrine, norepinephrine, dopamine) were used in the first postoperative days (vasoactive inotropic score at 12 h: 6 [4-12]), while inodilators (dobutamine, levosimendan) later. Length of vasoactive support was 3 [2-4] days. Independent predictors of vasoactive use were: LUTX indication different from cystic fibrosis (p = .003), higher Oto score (p = .020), longer cold ischemia time (p = .031), but not preoperative cardiac catheterization. VASO+ patients showed concomitant hemodynamic and graft impairment, with longer mechanical ventilation (p = .010), higher primary graft dysfunction (PGD) grade at 72 h (PGD grade > 0 65% vs. 31%, p = .004, OR 4.2 [1.54-11.2]), longer ICU (p < .001) and hospital stay (p = .013). Levosimendan as a second-line inodilator appeared safe. CONCLUSIONS: Vasoactive support is frequently necessary after LUTX, especially in recipients of grafts of lesser quality. Postoperative hemodynamic dysfunction requiring vasopressor support and graft dysfunction may represent a clinical continuum with immediate and long-term consequences. Further studies may elucidate if this represents a possible treatable condition.

Improving the prognostic value of multimorbidity through the integration of selected biomarkers to the comprehensive geriatric assessment: An observational retrospective monocentric study.

Background: Multimorbidity (MM) burdens individuals and healthcare systems, since it increases polypharmacy, dependency, hospital admissions, healthcare costs, and mortality. Several attempts have been made to determine an operational definition of MM and to quantify its severity. However, the lack of knowledge regarding its pathophysiology prevented the estimation of its severity in terms of outcomes. Polypharmacy and functional impairment are associated with MM. However, it is unclear how inappropriate drug decision-making could affect both conditions. In this context, promising circulating biomarkers and DNA methylation tools have been proposed as potential mortality predictors for multiple age-related diseases. We hypothesize that a comprehensive characterization of patients with MM that includes the measure of epigenetic and selected circulating biomarkers in the medical history, in addition to the functional capacity, could improve the prognosis of their long-term mortality. Methods: This monocentric retrospective observational study was conducted as part of a project funded by the Italian Ministry of Health titled "imProving the pROgnostic value of MultimOrbidity through the inTegration of selected biomarkErs to the comprehensive geRiatric Assessment (PROMOTERA)." This study will examine the methylation levels of thousands of CpG sites and the levels of selected circulating biomarkers in the blood and plasma samples of older hospitalized patients with MM (n = 1,070, age ≥ 65 years) recruited by the Reportage Project between 2011 and 2019. Multiple statistical approaches will be utilized to integrate newly measured biomarkers into clinical, demographic, and functional data, thus improving the prediction of mortality for up to 10 years. Discussion: This study's results are expected to: (i) identify the clinical, biological, demographic, and functional factors associated with distinct patterns of MM; (ii) improve the prognostic accuracy of MM patterns in relation to death, hospitalization-related outcomes, and onset of new comorbidities; (iii) define the epigenetic signatures of MM; (iv) construct multidimensional algorithms to predict negative health outcomes in both the overall population and specific disease and functional patterns; and (v) expand our understanding of the mechanisms underlying the pathophysiology of MM.

Association of COVID-19 Vaccinations With Intensive Care Unit Admissions and Outcome of Critically Ill Patients With COVID-19 Pneumonia in Lombardy, Italy.

Importance: Data on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2-related pneumonia are scarce. Objective: To evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU. Design, Setting, and Participants: This retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021. Exposures: COVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine). Main Outcomes and Measures: The incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders. Results: Among the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] age was 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dose was 0.03 (95% CI, 0.03-0.04; P < .001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P < .001). There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period: 139 patients (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Compared with unvaccinated patients, vaccinated patients were older (median [IQR]: 72 [66-76] vs 60 [51-69] years; P < .001), primarily male individuals (110 patients [79.1%] vs 252 patients [60.9%]; P < .001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P < .001) and had higher ratio of arterial partial pressure of oxygen (Pao2) and fraction of inspiratory oxygen (FiO2) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P = .007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower Pao2/FiO2 at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients. Conclusions and Relevance: In this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status. These findings suggest a substantial reduction of the risk of developing COVID-19-related severe acute respiratory failure requiring ICU admission among vaccinated people.

Sarcopenia in idiopathic pulmonary fibrosis: a prospective study exploring prevalence, associated factors and diagnostic approach.

BACKGROUND: Sarcopenia gained importance in the evaluation of patients with chronic respiratory diseases, including idiopathic pulmonary fibrosis (IPF), since it may impact negatively on clinical outcomes. AIM: Aim of this study is to evaluate the prevalence and factors associated with sarcopenia, defined according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) 2019 definition, and to evaluate the prevalence of the single criteria that define the EWGSOP2 definition (muscle strength, muscle quantity and physical performance), in a cohort of consecutive patients with IPF prospectively followed up in 9 hospitals in Northern Italy between December 2018 and May 2021. METHODS: Enrolled patients underwent an extensive pulmonary and nutritional assessment, including bioelectrical impedance analysis, dynamometry and 4-m gait speed test, both at IPF diagnosis and at 6-month follow-up. RESULTS: Out of the 83 patients (81% males, mean age 72.5 years) with IPF at disease diagnosis enrolled in the study, 19 (22.9%) showed sarcopenia, including 2 (2.4%) with severe sarcopenia, 5 (6.0%) with confirmed sarcopenia and 12 (14.5%) with probable sarcopenia. Sarcopenia was associated with a significantly higher severity of the disease and sedentary lifestyle, while no differences were observed in regards to body mass index, history of weight loss and comorbidities between patients with and without sarcopenia. Out of the 64 patients without sarcopenia at baseline, 16 cases showed alteration of muscle quantity and/or physical performance. In the 51 patients with complete data at 6-month follow-up, there were no cases of severe sarcopenia, 1 case (2.0%) showed confirmed sarcopenia, while the prevalence of probable sarcopenia was 19.6% (10 cases). No differences in regards to antifibrotic treatment received and onset of gastrointestinal side effects were observed between patients with and without sarcopenia at follow-up. CONCLUSIONS: The prevalence of sarcopenia in patients with IPF both at diagnosis and at 6-month follow-up was low but not negligible and was associated with higher severity of the disease and sedentary lifestyle. In IPF patients, a comprehensive diagnostic work-up including all the criteria defining the EWGSOP2 definition might be more useful than a series testing for prompt recognition of nutritional and physical performance abnormalities.

Longitudinal assessment of renal function after lung transplantation for cystic fibrosis: transition from post-operative acute kidney injury to acute kidney disease and chronic kidney failure.

INTRODUCTION: The clinical trajectory of post-operative acute kidney injury (AKI) following lung transplantation for cystic fibrosis is unknown. METHODS: Incidence and risk factors for post-operative AKI, acute kidney disease (AKD) and chronic kidney disease (CKD) were retrospectively analyzed in cystic fibrosis patients undergoing lung transplantation. Logistic regressions, Chi-square, Cuzick rank tests, and Cox-proportional hazard models were used. RESULTS: Eighty-three patients were included. Creatinine peaked 3[2-4] days after transplantation, with 15(18%), 15(18%), and 20(24%) patients having post-operative AKI stages 1, 2, and 3, while 15(18%), 19(23%) and 10(12%) developed AKD stage 1, stage 2 and 3, respectively. Higher AKI stage was associated with worsening AKD (p = 0.009) and CKD (p = 0.015) stages. Of the 50 patients with AKI, 32(66%) transitioned to AKD stage > 0, and then 27 (56%) to CKD stage > 1. Female sex, extracorporeal membrane oxygenation support as a bridge to lung transplant and at the end of the surgery, the use of intraoperative blood components, and cold-ischemia time were associated with increased risk of post-operative AKI and AKD. Higher AKI stage prolonged invasive mechanical ventilation (p = 0.0001), ICU stay (p = 0.0001), and hospital stay (p = 0.0001), and increased the incidence of primary graft dysfunction (p = 0.035). Both AKI and AKD stages > 2 worsened long-term survival with risk ratios of 3.71 (1.34-10.2), p = 0.0131 and 2.65(1.02-6.87), p = 0.0443, respectively. DISCUSSION: AKI is frequent in cystic fibrosis patients undergoing lung transplantation, it often evolves to AKD and to chronic kidney disease, thereby worsening short- and long-term outcomes.

Hematopoietic progenitor cell liabilities and alarmins S100A8/A9-related inflammaging associate with frailty and predict poor cardiovascular outcomes in older adults.

Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular disease and death. The mechanisms linking frailty and cardiovascular outcomes are mostly unknown. Here, we studied the association of abundance (flow cytometry) and gene expression profile (RNAseq) of stem/progenitor cells (HSPCs) and molecular markers of inflammaging (ELISA) with the cardiorespiratory phenotype and prospective adverse events of individuals classified according to levels of frailty. Two cohorts of older adults were enrolled in the study. In a cohort of pre-frail 35 individuals (average age: 75 years), a physical frailty score above the median identified subjects with initial alterations in cardiorespiratory function. RNA sequencing revealed S100A8/A9 upregulation in HSPCs from the bone marrow (>10-fold) and peripheral blood (>200-fold) of individuals with greater physical frailty. Moreover higher frailty was associated with increased alarmins S100A8/A9 and inflammatory cytokines in peripheral blood. We then studied a cohort of 104 more frail individuals (average age: 81 years) with multidomain health deficits. Reduced levels of circulating HSPCs and increased S100A8/A9 concentrations were independently associated with the frailty index. Remarkably, low HSPCs and high S100A8/A9 simultaneously predicted major adverse cardiovascular events at 1-year follow-up after adjustment for age and frailty index. In conclusion, inflammaging characterized by alarmin and pro-inflammatory cytokines in pre-frail individuals is mirrored by the pauperization of HSPCs in frail older people with comorbidities. S100A8/A9 is upregulated within HSPCs, identifying a phenotype that associates with poor cardiovascular outcomes.

Occupational Exposure in the Lombardy Region (Italy) to SARS-CoV-2 Infection: Results from the MUSTANG-OCCUPATION-COVID-19 Study.

Sero-epidemiological surveys are valuable attempts to estimate the circulation of SARS-CoV-2 in general or selected populations. Within this context, a prospective observational study was conducted to estimate the prevalence and persistence of SARS-CoV-2 antibodies in different categories of workers and factors associated with positivity, through the detection of virus-specific immunoglobulin G and M (IgG/IgM) in serum samples. Enrollees were divided in low exposure and medium-high groups on the basis of their work activity. Antibody responders were re-contacted after 3 months for the follow-up. Of 2255 sampled workers, 4.8% tested positive for SARS-CoV-2 IgG/IgM antibodies, with 81.7% to IgG only. Workers who continued to go to their place of work, were healthcare workers, or experienced at least one COVID-19-related symptom were more likely to test positive for SARS-CoV-2 antibodies. SARS-CoV-2 antibodies prevalence was significantly higher in the medium-high risk vs. low-risk group (7.2% vs. 3.0%, p < 0.0001). At 3-month follow-up, 81.3% of subjects still had antibody response. This study provided important information of SARS-CoV-2 infection prevalence among workers in northern Italy, where the impact of COVID-19 was particularly intense. The presented surveillance data give a contribution to refine current estimates of the disease burden expected from the SARS-CoV-2.

The natural history of idiopathic pulmonary fibrosis in a large European population: the role of age, sex and comorbidities.

Placebo arms of clinical trials provide an opportunity to investigate the natural history of idiopathic pulmonary fibrosis (IPF) but these patients are not representative of the real life IPF population. Objective of this article is to evaluate patients' characteristics of incident IPF cases and their impact on mortality and hospitalizations risk. We conducted a retrospective cohort study using data from administrative databases from 2000 to 2010. Based on different algorithms reported in literature, incident IPF cases were identified. We applied Cox proportional hazards models to assess relationship between patients' characteristics, mortality and hospitalization. According to three case definitions, we identified 2338, 460 and 1704 incident IPF cases. Mean age at diagnosis was about 72 years, the proportion of male varied between 59 and 62% and patients with at least one chronic disease were between 70 and 74%. Age, male sex and comorbidities were associated to worse outcomes. Congestive heart failure (CHF), diabetes and cancer were conditions associated to mortality, while those associated to hospitalization were CHF and chronic obstructive pulmonary disease. Our data source provided one of the largest samples of unselected patients with a long follow-up period. Using different algorithms proposed and validated in literature, we observed that mortality and hospitalization rate are high in patients with IPF and age, sex and comorbidities significantly affect clinical outcomes. Females show a significant survival advantage over males, even after adjusting for age and comorbidities. Patients with pre-existing diseases, especially those with pulmonary and cardiovascular diseases are at higher risk.

Emotional status and fear in patients scheduled for elective surgery during COVID-19 pandemic: a nationwide cross-sectional survey (COVID-SURGERY).

BACKGROUND: Fragmented data exist on the emotional and psychological distress generated by hospital admission during the pandemic in specific populations of patients, and no data exists on patients scheduled for surgery. The aim of this multicentre nationwide prospective cross-sectional survey was to evaluate the impact of pandemic on emotional status and fear of SARS-CoV-2 contagion in a cohort of elective surgical patients in Italy, scheduled for surgery during the COVID-19 pandemic. RESULTS: Twenty-nine Italian centres were involved in the study, for a total of 2376 patients surveyed (mean age of 58 years ± 16.61; 49.6% males). The survey consisted of 28 total closed questions, including four study outcome questions. More than half of patients had at least one chronic disease (54%), among which cardiovascular diseases were the commonest (58%). The most frequent type of surgery was abdominal (20%), under general anaesthesia (64%). Almost half of the patients (46%) declared to be frightened of going to the hospital for routine checkups; 55% to be afraid of getting SARS-CoV-2 infection during hospitalization and 62% were feared of being hospitalised without seeing family members. Having an oncological disease and other patient-related, centre-related or perioperative factors were independently associated with an increased risk of fear of SARS-CoV-2 infection during hospitalization and of being hospitalised without seeing family members. A previous infection due to SARS-COV-2 was associated with a reduced risk of worse emotional outcomes and fear of SARS-CoV-2 infection during hospitalization. Patients who showed the most emotionally vulnerable profile (e.g. use of sleep-inducing drugs, higher fear of surgery or anaesthesia) were at higher risk of worse emotional status towards the hospitalization during COVID-19 pandemic. Being operated in hospitals with lower surgical volume and with COVID-19 wards was associated with worse emotional status and fear of contagion. CONCLUSIONS: Additional fear and worse emotional status may be frequent in patients scheduled for elective surgery during COVID-19 pandemic. More than half of the participants to the survey were worried about not being able to receive family visits. Psychological support may be considered for patients at higher risk of psychological distress to improve perioperative wellbeing during the pandemic.

High-flow nasal oxygen versus noninvasive ventilation in adult patients with cystic fibrosis: a randomized crossover physiological study.

BACKGROUND: Noninvasive ventilation (NIV) is the first-line treatment of adult patients with exacerbations of cystic fibrosis (CF). High-flow nasal oxygen therapy (HFNT) might benefit patients with hypoxemia and can reduce physiological dead space. We hypothesized that HFNT and NIV would similarly reduce work of breathing and improving breathing pattern in CF patients. Our objective was to compare the effects of HFNT versus NIV in terms of work of breathing, assessed noninvasively by the thickening fraction of the diaphragm (TFdi, measured with ultrasound), breathing pattern, transcutaneous CO2 (PtcCO2), hemodynamics, dyspnea and comfort. METHODS: Adult CF patients who had been stabilized after requiring ventilatory support for a few days were enrolled and ventilated with HFNT and NIV for 30 min in crossover random order. RESULTS: Fifteen patients were enrolled. Compared to baseline, HFNT, but not NIV, reduced respiratory rate (by 3 breaths/min, p = 0.01) and minute ventilation (by 2 L/min, p = 0.01). Patients also took slightly larger tidal volumes with HFNT compared to NIV (p = 0.02). TFdi per breath was similar under the two techniques and did not change from baseline. MAP increased from baseline with NIV and compared to HFNT (p ≤ 0.01). Comfort was poorer with the application of both HFNT and NIV than baseline. No differences were found for heart rate, SpO2, PtcCO2 or dyspnea. CONCLUSIONS: In adult CF patients stabilized after indication for ventilatory support, HFNT and NIV have similar effects on diaphragmatic work per breath, but high-flow therapy confers additional physiological benefits by decreasing respiratory rate and minute ventilation. CLINICAL TRIAL REGISTRATION: Ethics Committee of St. Michael's Hospital (REB #14-338) and clinicaltrial.gov (NCT02262871).

Resolved versus confirmed ARDS after 24 h: insights from the LUNG SAFE study.

PURPOSE: To evaluate patients with resolved versus confirmed ARDS, identify subgroups with substantial mortality risk, and to determine the utility of day 2 ARDS reclassification. METHODS: Our primary objective, in this secondary LUNG SAFE analysis, was to compare outcome in patients with resolved versus confirmed ARDS after 24 h. Secondary objectives included identifying factors associated with ARDS persistence and mortality, and the utility of day 2 ARDS reclassification. RESULTS: Of 2377 patients fulfilling the ARDS definition on the first day of ARDS (day 1) and receiving invasive mechanical ventilation, 503 (24%) no longer fulfilled the ARDS definition the next day, 52% of whom initially had moderate or severe ARDS. Higher tidal volume on day 1 of ARDS was associated with confirmed ARDS [OR 1.07 (CI 1.01-1.13), P = 0.035]. Hospital mortality was 38% overall, ranging from 31% in resolved ARDS to 41% in confirmed ARDS, and 57% in confirmed severe ARDS at day 2. In both resolved and confirmed ARDS, age, non-respiratory SOFA score, lower PEEP and P/F ratio, higher peak pressure and respiratory rate were each associated with mortality. In confirmed ARDS, pH and the presence of immunosuppression or neoplasm were also associated with mortality. The increase in area under the receiver operating curve for ARDS reclassification on day 2 was marginal. CONCLUSIONS: ARDS, whether resolved or confirmed at day 2, has a high mortality rate. ARDS reclassification at day 2 has limited predictive value for mortality. The substantial mortality risk in severe confirmed ARDS suggests that complex interventions might best be tested in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02010073.

The association between air pollution and the incidence of idiopathic pulmonary fibrosis in Northern Italy.

Acute exacerbations and worsening of idiopathic pulmonary fibrosis (IPF) have been associated with exposure to ozone (O3), nitrogen dioxide (NO2) and particulate matter, but chronic exposure to air pollution might also affect the incidence of IPF. We investigated the association between chronic exposure to NO2, O3 and particulate matter with an aerodynamic diameter <10 µm (PM10) and IPF incidence in Northern Italy between 2005 and 2010.Daily predictions of PM10 concentrations were obtained from spatiotemporal models, and NO2 and O3 hourly concentrations from fixed monitoring stations. We identified areas with homogenous exposure to each pollutant. We built negative binomial models to assess the association between area-specific IPF incidence rate, estimated through administrative databases, and average overall and seasonal PM10, NO2, and 8-hour maximum O3 concentrations.Using unadjusted models, an increment of 10 µg·m-3 in NO2 concentration was associated with an increase between 7.93% (95% CI 0.36-16.08%) and 8.41% (95% CI -0.23-17.80%) in IPF incidence rate, depending on the season. After adjustment for potential confounders, estimated effects were similar in magnitude, but with larger confidence intervals.Although confirmatory studies are needed, our results trace a potential association between exposure to traffic pollution and the development of IPF.

Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study.

PURPOSE: To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality. METHODS: The large observational study to understand the global impact of severe acute respiratory failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across five continents. A pre-specified secondary aim was to examine the factors associated with outcome. Analyses were restricted to patients (93.1 %) fulfilling ARDS criteria on day 1-2 who received invasive mechanical ventilation. RESULTS: 2377 patients were included in the analysis. Potentially modifiable factors associated with increased hospital mortality in multivariable analyses include lower PEEP, higher peak inspiratory, plateau, and driving pressures, and increased respiratory rate. The impact of tidal volume on outcome was unclear. Having fewer ICU beds was also associated with higher hospital mortality. Non-modifiable factors associated with worsened outcome from ARDS included older age, active neoplasm, hematologic neoplasm, and chronic liver failure. Severity of illness indices including lower pH, lower PaO2/FiO2 ratio, and higher non-pulmonary SOFA score were associated with poorer outcome. Of the 578 (24.3 %) patients with a limitation of life-sustaining therapies or measures decision, 498 (86.0 %) died in hospital. Factors associated with increased likelihood of limitation of life-sustaining therapies or measures decision included older age, immunosuppression, neoplasia, lower pH and increased non-pulmonary SOFA scores. CONCLUSIONS: Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS. TRIAL REGISTRATION: ClinicalTrials.gov NCT02010073.

Epidemiology of Idiopathic Pulmonary Fibrosis in Northern Italy.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of idiopathic interstitial pneumonia. Despite its clinical relevance, few studies have examined the epidemiology of IPF and temporal variation in disease incidence and prevalence. Aim of the study was to investigate the prevalence, incidence and trends of IPF in Lombardy, a region with nearly 10 million inhabitants, during 2005-2010. METHODS: For the identification of IPF patients, we used healthcare administrative databases of Lombardy Healthcare System and adopted three algorithms: generic, broad and narrow case definition (GCD, BCD, NCD). IPF cases were identified according to diagnoses reported in inpatient and outpatient claims occurred during 2000-2010. We estimated age- and sex-adjusted annual prevalence and incidence rates from 2005 to 2010, thus allowing for a 5-year washout period. RESULTS: The mean annual incidence rate was estimated at 2.3 and 5.3 per 100,000 person-years using NCD and GCD, respectively. IPF incidence was higher among males, and increased with age. Trend remained stable over the years. The estimated annual prevalence rate was 35.5, 22.4, and 12.6 per 100,000 person-years using GCD, BCD and NCD, respectively, and increased with age. Moreover, we observed a positive trend over the years. Using BCD and NCD, prevalence was higher among males. CONCLUSIONS: The results of this study, which is one of the largest population-based survey ever conducted according to strict criteria, indicated that prevalence of IPF increased across the years while incidence remained stable, thus suggesting that survival with IPF has improved.

Epidemiological studies in idiopathic pulmonary fibrosis: pitfalls in methodologies and data interpretation.

Data on incidence, prevalence and mortality of idiopathic pulmonary fibrosis (IPF) are sparse and vary across studies. The true incidence and prevalence of the disease are unknown. In general, the overall prevalence and incidence reported in European and Asian countries are lower than those reported in American studies. In recent years, the epidemiological approach to IPF has been difficult for many reasons. First, the diagnostic criteria of the disease have changed over time. Secondly, the coding system used for IPF in administrative databases, the most common data source used to study this aspect of the disease, has been modified in the past few years. Finally, the study design, the methodology and the population selected in each of the studies are very different. All these aspects make comparisons among studies very difficult or impossible. In this review, we list the main issues that might arise when comparing different studies and that should be taken into consideration when describing the state of epidemiological knowledge concerning this pathology.

Pulmonary hypertension in idiopathic pulmonary fibrosis does not influence six-minute walk distance: results from a retrospective study.

BACKGROUND: The characteristics of the six-minute walk test (6MWT) in patients with idiopathic pulmonary fibrosis (IPF) and pulmonary hypertension (PH) have not yet been described; nevertheless, this test has already been used as a "surrogate end point" in some clinical trials. OBJECTIVE: Goal of this retrospective study was to assess whether the presence of PH in patients with IPF might influence 6MWT performances. METHODS: We retrospectively reviewed the data of patients with IPF who were referred to our hospital. The study population was divided in two groups according to the presence or absence of PH at right heart catheterization; then, the six-minute walking distance (6MWD) and pulmonary function tests (PFTs) were compared between groups. RESULTS: Study population included 30 IPF patients with a mean age of 59.0 years (± 8.3), most of whom (76.7%) were males. A total of 43.3% of patients had PH. PFTs data were similar in IPF patients of the two groups; the only exception was FVC, which was significantly higher in IPF patients with PH (63.8% ± 16.0 vs. 51.6% ± 13.8 in patients without PH, p<0.05). No difference was detected between groups in 6MWD (222.3m ± 118.5 in PH group and 222.1m ± 118.5 in non-PH group, p>0.05). CONCLUSIONS: Our data suggested that 6MWD does not differ between IPF patients with or without PH. Thus, 6MWD should not be used as a surrogate endpoint in clinical study in patients affected by IPF and PH.