Mortality trends in idiopathic pulmonary fibrosis in Europe between 2013 and 2018.

INTRODUCTION: Previous research has suggested that the incidence of idiopathic pulmonary fibrosis (IPF) is increasing in the United Kingdom (UK) and elsewhere. The aim of this study is to provide contemporary estimates of IPF mortality rates across 24 European Countries from 2013 to 2018, using death certificates data from the European Statistics Institution (EUROSTAT) database. METHODS: We extracted country data for IPF (International Classification of Diseases 10th Edition, ICD-10, code "J84.1") mortality from the EUROSTAT dataset. We calculated country- age- and sex-specific death registration rates between 2013 and 2018. We used direct standardisation to compare rates between countries. We calculated annual trends in mortality rate ratios using a segmented regression model. RESULTS: The overall standardised mortality rate in EU Countries during this period was 3.90 per 10 0000 person-years (95%, CI 3.80-3.90), with the rate raising from 3.70 in the 2013 to 4.00 in the 2018 (average annual percent change: 1.74%, 95% CI 0.91-2.59). We observed substantial inter-country differences, with the highest rates detected in Ireland, the UK, and Finland, the lowest rate in Bulgaria, and middle rates in Germany, Greece, Italy, the Netherlands, Portugal, and Slovenia. CONCLUSION: In summary, the IPF mortality rate is increasing across Europe. There are currently more than 17 000 deaths recorded from IPF each year in Europe but the marked geographical differences we observed suggest that this figure may underestimate the true rate considerably.

Malignant pleural effusion: current understanding and therapeutic approach.

Malignant pleural effusion (MPE) is a common complication of thoracic and extrathoracic malignancies and is associated with high mortality and elevated costs to healthcare systems. Over the last decades the understanding of pathophysiology mechanisms, diagnostic techniques and optimal treatment intervention in MPE have been greatly advanced by recent high-quality research, leading to an ever less invasive diagnostic approach and more personalized management. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy. In the next future, because of a better understanding of underlying tumor biology together with more sensitive molecular diagnostic techniques, it is likely that combined diagnostic and therapeutic procedures allowing near total outpatient management of MPE will become popular. This article provides a review of the current advances, new discoveries and future directions in the pathophysiology, diagnosis and management of MPE.

ERS/ESTS statement on the management of pleural infection in adults.

Pleural infection is a common condition encountered by respiratory physicians and thoracic surgeons alike. The European Respiratory Society (ERS) and European Society of Thoracic Surgeons (ESTS) established a multidisciplinary collaboration of clinicians with expertise in managing pleural infection with the aim of producing a comprehensive review of the scientific literature. Six areas of interest were identified: 1) epidemiology of pleural infection, 2) optimal antibiotic strategy, 3) diagnostic parameters for chest tube drainage, 4) status of intrapleural therapies, 5) role of surgery and 6) current place of outcome prediction in management. The literature revealed that recently updated epidemiological data continue to show an overall upwards trend in incidence, but there is an urgent need for a more comprehensive characterisation of the burden of pleural infection in specific populations such as immunocompromised hosts. There is a sparsity of regular analyses and documentation of microbiological patterns at a local level to inform geographical variation, and ongoing research efforts are needed to improve antibiotic stewardship. The evidence remains in favour of a small-bore chest tube optimally placed under image guidance as an appropriate initial intervention for most cases of pleural infection. With a growing body of data suggesting delays to treatment are key contributors to poor outcomes, this suggests that earlier consideration of combination intrapleural enzyme therapy (IET) with concurrent surgical consultation should remain a priority. Since publication of the MIST-2 study, there has been considerable data supporting safety and efficacy of IET, but further studies are needed to optimise dosing using individualised biomarkers of treatment failure. Pending further prospective evaluation, the MIST-2 regimen remains the most evidence based. Several studies have externally validated the RAPID score, but it requires incorporating into prospective intervention studies prior to adopting into clinical practice.

Early administration of tofacitinib in COVID-19 pneumonitis: An open randomised controlled trial.

BACKGROUND: Controversies on sub-populations most sensitive to therapy and the best timing of starting the treatment still surround the use of immunomodulatory drugs in COVID-19. OBJECTIVES: We designed a multicentre open-label randomised controlled trial to test the effect of prompt adding of tofacitinib to standard therapy for hospitalised patients affected by mild/moderate COVID-19 pneumonitis. METHODS: Patients admitted to three Italian hospitals affected by COVID-19 pneumonitis not requiring mechanical ventilation were randomised to receive standard treatment alone or tofacitinib (10 mg/bid) for 2 weeks, starting within the first 24 h from admission. RESULTS: A total of 116 patients were randomised; 49 in the experimental arm completed the 14-day treatment period, 9 discontinued tofacitinib as the disease worsened and were included in the analysis, and 1 died of respiratory failure. All 58 control patients completed the study. Clinical and demographic characteristics were similar between the study groups. In the tofacitinib group, 9/58 (15.5%) patients progressed to noninvasive ventilation (CPAP) to maintain SO2 > 93%, invasive mechanical ventilation or death by day 14 was 15.5%, significantly less than in the control group (20/58, 34.4%, RR 0,45, RRR -55%, NNT 5; p = .018). No differences in severe adverse effect incidence had been observed across the groups. CONCLUSION: High-dose tofacitinib therapy in patients with COVID pneumonitis is safe and may prevent deterioration to respiratory failure.

Effectiveness and economic impact of Dupilumab in asthma: a population-based cohort study.

RATIONALE: Severe asthma is burdened by relevant socio-economic and clinical impact. Randomized controlled trials on Dupilumab showed efficacy and a good safety profile, but post-market studies are needed. OBJECTIVES: To evaluate the impact of Dupilumab on (i) the use of anti-asthmatic drugs, including oral corticosteroids (OCS), (ii) the rates of asthma exacerbation-related hospital admissions, and (iii) the healthcare costs in patients with asthma. METHODS: Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). We compared healthcare resources use between the 6 months after Dupilumab initiation ("post-intervention period") and (i) the 6 months before Dupilumab initiation ("wash-out period") and (ii) the corresponding 6 months of the prior year ("pre-intervention period"). MAIN RESULTS: In a cohort of 176 patients, Dupilumab significantly reduced anti-asthmatic drugs use (including OCS and short-acting ß2-agonists, inhaled corticosteroids (ICS)/long-acting ß2-agonists and ICS alone) when comparing the "pre-intervention" to the "post-intervention" period. When considering hospital admissions, we observed a not statistically or marginally significant reduction between both periods before Dupilumab and the post-intervention period. Six-months discontinuation rate was 8%. Overall healthcare costs had a tenfold increase between the "pre-intervention" and "post-intervention" period, which was mainly led by the biologic drug cost. Conversely, expenditures connected to hospital admissions did not change. CONCLUSIONS: Our real-world investigation suggests that Dupilumab reduced anti-asthmatic drugs use, including OCS, in comparison to a corresponding period in the prior year. However, long-term healthcare sustainability remains an open issue.

Historical eye: from traditional to endobronchial ultrasound-guided needle aspiration and beyond.

PURPOSE OF REVIEW: In the history of bronchoscopy, the advent of flexible transbronchial needle aspiration (TBNA) before and, subsequently, of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), have represented fundamental events, as they have significantly and definitively changed interventional pulmonology's role in diagnostic and therapeutic work-up of most of thoracic diseases.Purpose of this historical review is to retrace the main stages that have contributed to the development of these two techniques. RECENT FINDINGS: TBNA allowed the bronchoscopists to overcome the barrier of the tracheobronchial wall and to obtain samples from hilar-mediastinal lesions. With this additional method, bronchoscopy has become an essential procedure for staging of lung cancer.The advent of echo-bronchoscopes, allowing to perform TBNA under direct ultrasound guidance in real time, further increased the diagnostic yield of this technique. Furthermore, the insertion of the echo-bronchoscope through the oesophagus allowed to extend the landscape of targets to sample, including also para-esophageal lesions, liver metastases, celiac nodes and left adrenal glands.EBUS-TBNA has shown its usefulness not only in the approach to mediastinal lesions, but also in other clinical conditions, such as lung nodules or masses adjacent to the tracheobronchial tree. SUMMARY: Despite the obvious advantages of EBUS-TBNA, this technology is not yet available in many centres and countries worldwide. For this reason, TBNA remains a basic technique that must complete the technical background of bronchoscopists and it should not be forgotten.

Efficacy of Small versus Large-Bore Chest Drain in Pleural Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Pleural infection represents a significant clinical challenge worldwide. Although prompt drainage of pleural fluid is thought to play a key role in pleural infection management, the optimal size of intrapleural catheter has yet to be defined. OBJECTIVES: The aim of this systematic review and meta-analysis was to summarize data on efficacy and complications of small-bore drain (SBD), defined as ≤14F, in comparison to large-bore drain (LBD) in patients with pleural infection. METHOD: We searched MEDLINE and Embase for all studies reporting outcomes of interest published up to October 2021. Two authors reviewed selected full text to identify studies according to predefined eligibility criteria. Summary estimates were derived using the random-effects model. RESULTS: Twelve original studies were included for qualitative analysis and 7 of these for quantitative analysis. The surgical referral rate of SBD and LBD were, respectively, 0.16 (95% confidence interval [CI], 0.12-0.21) and 0.20 (95% CI, 0.10-0.32), the pooled mortality were 0.12 (95% CI, 0.05-0.21) and 0.20 (95% CI, 0.10-0.32), and the length of hospital stay was 24 days in both groups. Data on complications suggest similar proportions of tube dislodgement. Intensity of pain was evaluated in one study only, reporting higher scores for LBD. CONCLUSIONS: This systematic review and meta-analysis provide the first synthesis of data on performance of SBD and LBD in management of pleural infection, and, overall, clinical outcomes and complications did not substantially differ, although the limited number of studies and the absence of dedicated randomized trials does limit the reliability of results.

Long-term effects of air pollutants on respiratory and cardiovascular mortality in a port city along the Adriatic sea.

BACKGROUND: Shipping and port-related air pollution has a significant health impact on a global scale. The present study aimed to assess the mortality burden attributable to long-term exposure to ambient particulate matter (PM2.5, PM10) and nitrogen dioxide (NO2) in the city of Ancona (Italy), with one of the leading national commercial harbours. METHODS: Exposure to air pollutants was derived by dispersion models. The relationship between the long-term exposure of air pollution exposure and cause-specific mortality was evaluated by Poisson regression models, after adjustment for gender, age and socioeconomic status. Results are expressed as percent change of risk (and relative 95% confidence intervals) per 5 unit increases in the exposures. The health impact on the annual number of premature cause-specific deaths was also assessed. RESULTS: PM2.5 and NO2 annual concentrations were higher in the area close to the harbour than in the rest of the city. Positive associations between each pollutant and most of the mortality outcomes were observed, with estimates of up to 7.6% (95%CI 0.1, 15.6%) for 10 µg/m3 increase in NO2 and cardiovascular mortality and 15.3% (95%CI-1.1, 37.2%) for 10 µg/m3 increase PM2.5 and lung cancer. In the subpopulation living close to the harbour, there were excess risks of up to 13.5%, 24.1% and 37.9% for natural, cardiovascular and respiratory mortality. The number of annual premature deaths due to the excess of PM2.5 and NO2 exposure (having as a reference the 2021 World Health Organization Air Quality Guidelines) was 82 and 25, respectively. CONCLUSIONS: Our study confirms the long-term health effects of PM and NO2 on mortality and reveals a higher mortality burden in areas close to shipping and port-related emissions. Estimating the source-specific health burdens is key to achieve a deeper understanding of the role of different emission sources, as well as to support effective and targeted mitigation strategies.

Management of malignant pleural effusion in Italian clinical practice: a nationwide survey.

BACKGROUND: Pleural disease (PD), particularly malignant pleural effusion (MPE), is a common cause of hospital admission and its prevalence is rising worldwide. Recent advances in diagnostic and therapeutic options, such as Indwelling Pleural Catheters (IPCs), have simplified PD treatment, allowing an effective outpatients management. Therefore, dedicated pleural services can improve PD care, guaranteeing specialized management and optimizing time and cost. We aimed to provide an overview on MPE management in Italy, mainly focused on distribution and characteristics of pleural services and IPCs use. METHODS: A nationwide survey, endorsed by the Italian Thoracic Society, was distributed by email to members of selected subgroups in 2021. RESULTS: Ninety (23%) members replied, most of whom being pulmonologists (91%). MPE resulted the most common cause of pleural effusion and was managed with heterogenous approaches, including talc pleurodesis via slurry (43%), talc poudrage (31%), repeated thoracentesis (22%) and IPCs insertion (2%). The setting of IPC insertion was inpatient care in 48% of cases, with a predominance of draining frequency every other day. IPC management mainly relied on caregivers (42%). The presence of a pleural service was reported by 37% of respondents. CONCLUSIONS: The present study provides an extensive overview of MPE management in Italy, showing a highly heterogeneous approach, a scarce prevalence of out-patient pleural services, and a still limited adoption of IPCs, mainly due to lack of dedicated community care systems. This survey emphasizes the need of promoting a higher spreading of pleural services and an innovative healthcare delivery with more favourable cost-benefit ratio.

Bronchoscopic diagnosis of peripheral lung lesions.

PURPOSE OF REVIEW: Over the last decades, in addition to the traditional fluoroscopy, various and innovative guidance systems have been adopted in clinical practice for transbronchial approach to peripheral pulmonary lesions (PPLs). The aim of this article is to summarize the most recent data on available guidance systems and sampling tools, evaluating also advantages and limitations of each technique. RECENT FINDINGS: Although several studies have been published over the last years, large randomized studies comparing the different techniques are scanty. Fluoroscopy is the traditional and still most widely utilized guidance system. New guidance systems (electromagnetic navigation bronchoscopy, ultrasound miniprobe, cone beam computed tomography) seems to provide a better sensitivity, especially for small lesions not visualized by fluoroscopy. Among the sampling instruments, there is a good evidence that flexible transbronchial needle provides the better diagnostic yield and that sensitivity may increase if more than one sampling instrument is used. SUMMARY: Even if great progress has been done since the first articles on the transbronchial approach to PPLs, better scientific evidence and more reliable randomized trials are needed to guide interventional pulmonologists in choosing the best technique according to different clinical scenarios and source availability.

Chronic obstructive pulmonary disease (COPD) mortality trends worldwide: An update to 2019.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) incidence, prevalence, mortality and socioeconomic burden are considerable and vary across countries. The aim of the present study was to update the analysis of COPD mortality worldwide using data from the World Health Organization (WHO) up to 2019. METHODS: We obtained COPD mortality and population data for 22 European countries and the European Union (EU) as a whole, 10 American countries and six other countries from the WHO mortality database. We calculated age-standardized mortality rates in both sexes and examined trends by country with joinpoint analysis between 1994 and 2019. RESULTS: Between 2005-2007 and 2015-2017, overall COPD mortality decreased in EU men (-16.3%) but increased in women (12.7%) to reach rates of 14.0/100,000 in men and of 6.4/100,000 in women. In the United States, mortality declined in men to 21.3/100,000 but rose in women to 18.3/100,000. Mortality declined in most Latin American countries and all Asian countries, while an increase in Australian women was observed. CONCLUSION: A steady decrease in COPD mortality was observed in most of countries for men, whilst a different trend was observed in women in several countries. These trends are largely explained by changes in smoking habits, with an additional contribution of air pollution and occupational exposures. Despite past and ongoing tobacco control initiatives, this condition still remains a leading cause of death, in particular in countries with lower socio-demographic indices.

Accuracy and Predictors of Success of EUS-B-FNA in the Diagnosis of Pulmonary Malignant Lesions: A Prospective Multicenter Italian Study.

BACKGROUND: The role of endoscopic ultrasound with bronchoscope fine-needle aspiration (EUS-B-FNA) in the diagnosis of suspected malignant pulmonary lesions adjacent to the esophagus has been poorly investigated. The aim of the present study was to assess the accuracy of EUS-B-FNA for the diagnosis and molecular profiling of paraesophageal pulmonary lesions, as well as its predictors of success. MATERIALS AND METHODS: Patients who underwent EUS-B-FNA for the diagnosis of paraesophageal lesions were consecutively enrolled in four Italian centers. Demographic, clinical, procedural, pathological, and molecular characteristics of the malignant samples were collected. The primary outcome was the diagnostic accuracy for pulmonary malignancies. Secondary outcomes were diagnostic yield and predictors of success for diagnosis and molecular profiling. RESULTS: 107 adult patients (60 [56.1%] males; median (interquartile range) age: 69 [60-70] years) were enrolled. The diagnostic accuracy of EUS-B-FNA was 95.3% in the overall cohort and 95.2% in the 99 patients with a final diagnosis of malignancy. Neither clinical nor procedural variables significantly affected the diagnostic accuracy, whereas rapid on-site evaluation (ROSE), performed by pathologists or trained pulmonologists, was a strong predictor for a complete molecular profiling (OR [95% CI]: 12.9 [1.2-137.4]; p value: 0.03). CONCLUSION: EUS-B-FNA is a safe and accurate method for the diagnosis of paraesophageal pulmonary lesions. The presence of ROSE is relevant for a complete molecular profiling in this selected cohort of patients with advanced lung cancer.

Long-term prognostic outcomes in patients with haemoptysis.

BACKGROUND: Haemoptysis is a challenging symptom that can be associated with potentially life-threatening medical conditions. Follow-up is key in these patients to promptly detect new or misdiagnosed pathologic findings. Few prospective studies have evaluated long-term prognostic outcomes in patients with haemoptysis. Furthermore, the role played by antiplatelet and anticoagulant drugs on mortality and recurrence rates is unclear. The aim of this study was to assess mortality after 18 months of follow-up. Furthermore, the incidence of recurrence and the risk factors for recurrence and death were evaluated (including the role played by anticoagulant and antiplatelet drugs). METHODS: Observational, prospective, multicentre, Italian study. RESULTS: 451/606 (74.4%) recruited patients with haemoptysis completed the 18 months follow-up. 22/604 (3.6%) diagnoses changed from baseline to the end of the follow-up. 83/604 (13.7%) patients died. In 52/83 (62.7%) patients, death was the outcome of the disease which caused haemoptysis at baseline. Only the diagnosis of lung neoplasm was associated with death (OR (95%CI): 38.2 (4.2-347.5); p-value: 0.0001). 166 recurrences were recorded in 103/604 (17%) patients. The diagnosis of bronchiectasis was significantly associated with the occurrence of a recurrence (OR (95% CI): 2.6 (1.5-4.3)); p-value < 0.0001). Anticoagulant, antiaggregant, and anticoagulant plus antiaggregant drugs were not associated with an increased risk of death and recurrence. CONCLUSIONS: Our study showed a low mortality rate in patients with haemoptysis followed-up for 18 months. Pulmonary malignancy was the main aetiology and the main predictor of death, whereas bronchiectasis was the most frequent diagnosis associated with recurrence. Antiplatelet and/or anticoagulant therapy did not change the risk of death or recurrence. Follow-up is recommended in patients initially diagnosed with lower airways infections and idiopathic bleeding. TRIAL REGISTRATION: NCT02045394.

Sarcoidosis and maligancy: the chicken and the egg?

PURPOSE OF REVIEW: There is a complex interaction between sarcoidosis and malignancy. Since tumors can elicit a granulomatous reaction, the presence of granulomas alone is insufficient to diagnose sarcoidosis in a patient with cancer. In addition, check point inhibitors can also lead to a granulomatous reaction which can be misdiagnosed as sarcoidosis. These issues need to be considered when exploring the relationship between sarcoidosis and malignancy. Despite these limitations, a growing amount of evidence supports the potential interaction of sarcoidosis and malignancy. RECENT FINDINGS: Several large epidemiologic studies of patients from Europe, the USA, and Japan reveal an increased relative risk for cancer in sarcoidosis patients. The highest relative risks are seen in patients with lymphoma and breast cancer. New criteria have been developed to standardize the diagnosis of sarcoidosis, which should further clarify the association. SUMMARY: The diagnosis of sarcoidosis may precede or occur after malignancy. In a sarcoidosis patient with an atypical lesion, such as a breast mass, a biopsy should be considered.

Intrapleural Foreign Body: Case Report.

The detection of foreign bodies in the pleural cavity is rare and mostly consequent to iatrogenic or traumatic events. The migration of an inhaled foreign body from the airways to the pleural space through a bronchopleural fistula is an exceptional event. We report a case of a pleural empyema consequent to an inhaled wooden skewer. CT scan and bronchoscopy were unable to identify the foreign body, due to its migration in the peripheral airways. The thin and pointed foreign body perforated the visceral pleural surface emerging in the pleural cavity.

Diagnostic Yield and Safety of Image-Guided Pleural Biopsy: A Systematic Review and Meta-Analysis.

BACKGROUND: Diagnostic yield (DY) and safety of computed tomography (CT)- and thoracic ultrasound (TUS)-guided biopsies in the diagnosis of pleural lesions have been investigated in a number of studies, but no synthesis of data from the literature has ever been performed. OBJECTIVES: We aimed to provide the first systematic review and meta-analysis on the DY and safety of CT- versus TUS-guided biopsy in the diagnosis of pleural lesions. METHOD: We searched MEDLINE and EMBASE for all studies reporting outcomes of interest published up to April 2018. Two authors reviewed all titles/abstracts and retrieved selected full text to identify studies according to predefined selection criteria. Summary estimates were derived using the random-effects model. Cumulative meta-analysis assessed the influence of increasing adoption of the procedures over time. RESULTS: Thirty original studies were included in the present review; the number of studies on TUS-guided biopsy was almost three-fold higher than those on CT-guided biopsy. The pooled DYs of the 2 procedures were overall excellent and differed <10%, being 84% for TUS-guided biopsy and 93% for CT-guided biopsy. Safety profiles were reassuring for both the techniques, being 7 and 3% for CT- and TUS-guided biopsy, respectively. DY of ultrasound technique significantly improved over time, while no time effect was observed for CT-guided biopsy. CONCLUSIONS: Data show that CT- and TUS-guided biopsies in the diagnosis of pleural lesions are both excellent procedures, without meaningful differences in DYs and safety. Considering that TUS is non-ionizing and easily performed at the bedside, it should be the preferred approach in presence of adequate skills.

Predictors of readmission requiring hospitalization after discharge from emergency departments in patients with COVID-19.

INTRODUCTION: Little is known on prevalence of early return hospital admission of subjects with COVID-19 previously evaluated and discharged from emergency departments (EDs). This study aims to describe readmission rate within 14 days of patients with COVID-19 discharged from ED and to identify predictors of return hospital admission. METHODS: We performed a retrospective cohort study of adult patients with COVID-19 discharged from two EDs. Return hospital admission was defined as an unscheduled return ED visit within 14 days after initial ED evaluation and discharge. We compared the group of patients who had a return hospital admission to those who did not. We also evaluated selected clinical characteristics (age, neutrophilia, SOFA, lactate dehydrogenase, C-reactive protein and D-dimer) associated with return hospital admission. RESULTS: Of 283 patients included in the study, 65 (22.9%) had a return ED visit within 14 days. 32 of those patients (11%) were then hospitalized, while the remaining 33 were again discharged. Patients requiring a return hospital admission was significantly older, had higher pro-calcitonin and D-dimer levels. Major predictors of return hospital admission were cognitive impairment (OR 17.3 [CI 4.7-63.2]), P/F < 300 mmHg (OR 8.6 [CI 1.6-44.3]), being resident in geriatric care facility (OR 7.6 [CI 2.1-26.4]) and neutrophilia (OR 5.8 [CI 1.6-22.0]). CONCLUSION: Several factors are associated with 14-day return hospital admission in COVID-19 subjects. These should be considered when assessing discharge risk in ED clinical practice.

Pleuroparenchymal fibroelastosis in systemic sclerosis: prevalence and prognostic impact.

Interstitial lung disease (ILD) in systemic sclerosis (SSc) is a major cause of morbidity and mortality, mostly presenting as non-specific interstitial pneumonia. Little is known about the prevalence of pleuroparenchymal fibroelastosis (PPFE), a specific entity affecting the visceral pleura and subpleural parenchyma. We set out to estimate PPFE prevalence in two large cohorts of SSc patients and to assess its impact on survival and functional decline.A total of 359 SSc patients, derived from two referral centres in two different countries (UK and Italy), were included. The first available high-resolution computed tomography scan was independently evaluated by two radiologists blind to clinical information, to quantify ILD extent, freestanding bronchial abnormalities, and lobar percentage involvement of PPFE on a four-point categorical scale. Discordant scores were adjudicated by a third scorer. PPFE extent was further classified as limited (≤2/18) or extensive (>2/18). Results were evaluated against functional decline and mortality.The overall prevalence of PPFE in the combined SSc population was 18% (11% with extensive PPFE), with no substantial difference between the two cohorts. PPFE was significantly linked to free-standing bronchial abnormalities (61% versus 25% in PPFE versus no PPFE; p<0.0001) and to worse survival, independently of ILD severity or short-term lung function changes (HR 1.89, 95% CI 1.10-3.25; p=0.005).In the current study, we provide an exhaustive description of PPFE prevalence and clinical impact in the largest cohort of SSc subjects published so far. PPFE presence should be carefully considered, due to its significant prognostic implications.

Increased prevalence of small airways dysfunction in patients with systemic sclerosis as determined by impulse oscillometry.

OBJECTIVES: The prevalence and clinical implications of small airways involvement in SSc are still to be fully elucidated. The goal of the present work is to assess the prevalence of small airways dysfunction by impulse oscillometry and to determine whether it correlates with selected disease-related features and respiratory-related quality of life. METHODS: Ninety-four SSc patients and 93 healthy controls were studied by impulse oscillometry measurements. Small airways dysfunction was defined as the difference between resistance at low frequency, i.e. 5 Hz, and resistance at high frequency, i.e. 20 Hz, termed 'R5-R20', ⩾0.07 kPa/l/s. The St George's Respiratory Questionnaire was used to measure health impairment in SSc patients. Radiological features of small airways disease and parenchymal abnormalities on high resolution CT chest scans were jointly assessed by two thoracic radiologists. RESULTS: Small airways dysfunction was present in 21.5% of the SSc patient cohort, with a prevalence almost 5-fold higher compared with controls, and it was significantly associated with worse respiratory-related quality of life. Radiological features consistent with small airways abnormalities were detected in 25% of SSc patients, mostly in the absence of interstitial lung changes. Combining functional and radiological evaluations, one-third of the SSc cohort showed at least one feature of small airways involvement, which was associated with the lcSSc phenotype and with longer disease duration. CONCLUSION: The current study strengthens the hypothesis that small airway dysfunction might be a feature of SSc-related lung involvement, providing the first data on its significant impact on respiratory-related quality of life. A full assessment of lung function in SSc patients should include impulse oscillometry as a complementary technique, due to potential clinical and therapeutic implications.

How the Pathological Microenvironment Affects the Behavior of Mesenchymal Stem Cells in the Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by fibroblasts activation, ECM accumulation, and diffused alveolar inflammation. The role of inflammation in IPF is still controversial and its involvement may follow nontraditional mechanisms. It is seen that a pathological microenvironment may affect cells, in particular mesenchymal stem cells (MSCs) that may be able to sustain the inflamed microenvironment and influence the surrounding cells. Here MSCs have been isolated from fibrotic (IPF-MSCs) and control (C-MSCs) lung tissue; first cells were characterized and compared by the expression of molecules related to ECM, inflammation, and other interdependent pathways such as hypoxia and oxidative stress. Subsequently, MSCs were co-cultured between them and with NHLF to test the effects of the cellular crosstalk. Results showed that pathological microenvironment modified the features of MSCs: IPF-MSCs, compared to C-MSCs, express higher level of molecules related to ECM, inflammation, oxidative stress, and hypoxia; notably, when co-cultured with C-MSCs and NHLF, IPF-MSCs are able to induce a pathological phenotype on the surrounding cell types. In conclusion, in IPF the pathological microenvironment affects MSCs that in turn can modulate the behavior of other cell types favoring the progression of IPF.