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Background and objective: In clinical practice, a working diagnosis of IPF may be performed to provide effective antifibrotic treatment to patients who cannot undergo SLB. In this study, we compared the disease course across IPF diagnostic categories in a real-life clinical setting to clarify the appropriateness of a working diagnosis of IPF and treatment initiation in these patients. Methods: Longitudinal data from IPF patients receiving antifibrotic treatment (pirfenidone or nintedanib) were retrospectively collected at three tertiary centres in Italy. Univariate and multivariate analyses were performed to compare time to death and to a composite endpoint of disease progression between two diagnostic subgroups, that is, patients with UIP on HRCT and/or SLB, and patients with possible UIP and no histological confirmation. Results: A total of 249 IPF patients were included in the analysis. Among patients with a possible UIP pattern on HRCT, 41 (55%) were prescribed antifibrotic treatment (either nintedanib or pirfenidone) despite absence of histological confirmation. This group demonstrated similar mortality and disease progression as compared to patients with a definite diagnosis of IPF as per diagnostic guidelines (log-rank test P = 0.771 and P = 0.139, respectively). Such findings were confirmed on multivariate analysis (HR: 1.19, 95% CI: 0.49–2.89, P = 0.7 for death; HR: 1.42, 95% CI: 0.83–2.44, P = 0.201 for disease progression). Conclusion: In patients receiving antifibrotics following a working diagnosis of IPF, disease progression rates were similar to patients with a confident diagnosis of IPF according to consensus guidelines, supporting the rationale for treatment initiation in these patients by expert multidisciplinary teams.

Introduction: Gender, age, physiology (GAP) system have proven to be an easy tool for predicting disease stages and survival in idiopathic pulmonary fibrosis (IPF) patients. Objective: To validate mortality risk as determined by the GAP system in a real-life multicentre IPF population treated with pirfenidone. Methods: The study included patients who received pirfenidone for at least 6 months. The GAP calculator and the GAP index were determined. The primary outcome was all-cause mortality. The prognostic accuracy of the GAP system was evaluated with respect to calibration and discrimination. Results and Conclusion: Sixty-eight IPF patients were enrolled in the study. The median follow-up was 2.4 years (range 0.1-7.4 years). A total of 22 deaths as first event (32%) and of 10 lung transplantation (15%) were recorded. The cumulative incidence of mortality at 1, 2 and 3 years was 10.4%, 22.4% and 38.4%, respectively. The differences between the predicted and observed mortality were not significant for the GAP index while the observed mortality become comparable to that predicted by the GAP calculator only in the third year of follow-up. The C-index for the GAP index was 0.74 (95% CI 0.57-0.93) while the C-statistic value for the GAP calculator was 0.77 (95% CI 0.59-0.95)

Several components of the respiratory system may be involved in multisystem diseases, such as the airways, vessels, parenchyma, pleura and respiratory muscles; in addition to the lungs, many other organs may also be involved. ILD, frequently detected in multisystem diseases, has a significant impact on morbidity and mortality in this heterogeneous group of diseases. In particular, many CTDs involve the lungs either directly or as a treatment complication. Pulmonary involvement, and particularly ILD, may be detected at any point in the natural history of a systemic disease. Therefore, a multidisciplinary approach is crucial in the diagnostic work-up, diagnostic/therapeutic decision making and during follow-up, enabling the input of different experts. This has become the current diagnostic reference standard for ILD and is reported to improve diagnostic confidence and agreement compared with the decisions of individual participants of the multidisciplinary discussion. However, many questions regarding the composition and governance of the multidisciplinary team remain unanswered, requiring further studies to better define the power of this tool with the aim of earlier and better-defined diagnosis, management and follow-up.

Rationale: In the INSTAGE trial in patients with idiopathic pulmonary fibrosis (IPF) and severely impaired gas exchange, nintedanib plus sildenafil was associated with numerical benefits on St. George's Respiratory Questionnaire (SGRQ) total score, brain natriuretic peptide (BNP), and FVC decline versus nintedanib alone. Exploratory analyses of the STEP-IPF (Sildenafil Trial of Exercise Performance in IPF) trial suggested that sildenafil may have a greater effect on SGRQ score in patients with IPF who have right heart dysfunction (RHD). Objectives: Assess whether RHD influenced the effects of nintedanib plus sildenafil versus nintedanib alone in the INSTAGE trial. Methods: Subgroup analyses of patients with (n = 117) versus those without (n = 156) echocardiographic signs of RHD at baseline. Measurements and Main Results: There was no heterogeneity between subgroups by presence of RHD in the effect of nintedanib plus sildenafil versus nintedanib alone on change in SGRQ total score at Week 12 (P = 0.74) or Week 24 (P = 0.90), or change in FVC at Week 12 (P = 0.58) or Week 24 (P = 0.55). In both subgroups, nintedanib plus sildenafil had a numerically greater effect on reducing FVC decline versus nintedanib alone. Between-group differences in change in BNP at Week 24 were 2119.9 ng/L (95% confidence interval = 2171.3 to 268.5) and 23.6 ng/L (95% confidence interval = 247.2 to 40.0) in patients with and without signs of RHD at baseline, respectively (P, 0.01). Conclusions: In the INSTAGE trial, there were no significant differences in the effects of nintedanib plus sildenafil versus nintedanib alone on changes in SGRQ and FVC between patients with or without echocardiographic signs of RHD at baseline. The benefit of combination therapy on stabilizing BNP was more pronounced in patients with RHD at baseline.

Rationale: Real-world data on pirfenidone treatment of patients with idiopathic pulmonary fibrosis (IPF) are limited. This study assessed the effectiveness of pirfenidone in a large real-life Italian IPF cohort. Methods: IRENE was an observational, retrospective study of patients with IPF treated with pirfenidone in routine clinical practice (18 centres). At Month 6, a mandatory re-evaluation of forced vital capacity (FVC) decline (absolute change < 10%) was required to continue pirfenidone. The primary effectiveness outcomes were absolute change from baseline in FVC and the percentage of patients with ≥ 10% absolute decline in % predicted FVC at Month 12. Safety was described by adverse event (AE) occurrence. Prespecified subgroups included sex, age, presence/absence of emphysema, usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography, and baseline lung function. Results: The study included 379 patients (mean age, 67.6 years; 78.1% male). Mean change from baseline in FVC and the percentage of patients with ≥ 10% absolute decline in % predicted FVC at Month 12 were −81.8 mL (SD, 419.6 mL; P = 0.002) and 16.0% (95% CI, 12.2–20.9%), respectively. Disease progression was similar across prespecified subgroups, including patients with definite vs possible UIP. Overall, 211 AEs occurred in 149 patients (39.3%), with serious AEs in 31 patients (8.2%) and 9 discontinuations due to AEs. Skin and gastrointestinal AEs were most frequent. Fifteen patients (4.0%) died. Conclusions: The decline in FVC and the safety profile observed in this real-world IPF cohort were consistent with the findings of the Phase III pirfenidone trials.

Acute exacerbation (AE) is a possible manifestation of interstitial lung diseases (ILD) associated to very high mortality. It’s defined as clinically significant respiratory deterioration with evidence of new widespread alveolar abnormalities on computed tomography scan. AE is better described in idiopathic pulmonary fibrosis (IPF) but also reported in ILD secondary to connective tissue diseases (CTD) and vasculitis. The main features and the real clinical impact of this severe complication in these patients are not well defined. Aim of our study was to prospectively investigate the incidence, clinical features and outcome of AE in a population of patients with ILD related to CTD and vasculitis. We consecutively enrolled all patients, with ILD secondary to rheumatic systemic diseases, referring to our multidisciplinary outpatient clinic for rare lung diseases. All patients were followed for at least 12 months (range, 12–36 months). At baseline, all patients underwent to a core set of laboratory investigations and periodically followed; data about demographic, disease onset, clinical, serological and therapeutic features were also recorded. AE occurred in 9/78 patients, with an incidence of 5.77/100 patients/year, and 5/9 patients died because of AE. The baseline value of DLCO was significantly associated to the risk of AE at Cox regression. In patients with ILD related to rheumatic systemic diseases AE can occur with an incidence similar to IPF. Rheumatologists should carefully consider this life-threatening complication as a possible natural course of all patients with ILD secondary to systemic rheumatic disease.

Background: "Velcro-type" crackles on chest auscultation are considered a typical acoustic finding of Fibrotic Interstitial Lung Disease (FILD), however whether they may have a role in the early detection of these disorders has been unknown. This study investigated how "Velcro-type" crackles correlate with the presence of distinct patterns of FILD and individual radiologic features of pulmonary fibrosis on High Resolution Computed Tomography (HRCT). Methods: Lung sounds were digitally recorded from subjects immediately prior to undergoing clinically indicated chest HRCT. Audio files were independently assessed by two chest physicians and both full volume and single HRCT sections corresponding to the recording sites were extracted. The relationships between audible "Velcro-type" crackles and radiologic HRCT patterns and individual features of pulmonary fibrosis were investigated using multivariate regression models. Results: 148 subjects were enrolled: bilateral "Velcro-type" crackles predicted the presence of FILD at HRCT (OR 13.46, 95% CI 5.85-30.96, p < 0.001) and most strongly the Usual Interstitial Pneumonia (UIP) pattern (OR 19.8, 95% CI 5.28-74.25, p < 0.001). Extent of isolated reticulation (OR 2.04, 95% CI 1.62-2.57, p < 0.001), honeycombing (OR 1.88, 95% CI 1.24-2.83, < 0.01), ground glass opacities (OR 1.74, 95% CI 1.29-2.32, p < 0.001) and traction bronchiectasis (OR 1.55, 95% CI 1.03-2.32, p < 0.05) were all independently associated with the presence of "Velcro-type" crackles. Conclusions: "Velcro-type" crackles predict the presence of FILD and directly correlate with the extent of distinct radiologic features of pulmonary fibrosis. Such evidence provides grounds for further investigation of lung sounds as an early identification tool in FILD.

Pirfenidone reduces functional decline in patients with Idiopathic Pulmonary Fibrosis (IPF). However, response to treatment is highly heterogeneous. We sought to evaluate whether response to pirfenidone is influenced by the pretreatment rate of forced vital capacity (FVC) decline. Fifty-six IPF patients were categorized as rapid (RP) or slow progressors (SP) based on whether their FVC decline in the year preceding pirfenidone treatment was > or ≤ 10% predicted. Following pirfenidone treatment patients were followed-up every 6 months and up to 24 months. In the entire population, pirfenidone reduced significantly FVC decline from 231 to 49 ml/year at 6 months (T6) (p = 0.003) and this effect was maintained at the 12-, 18- and 24-month time points (p value for trend n.s.). In RP, the reduction of FVC decline was evident at 6 months (36 vs 706 ml/year pretreatment; p = 0.002) and maintained, though to a lesser degree, at 12 (106 ml/year), 18 (176 ml/year) and 24 months (162 ml/year; p value for trend n.s). Among SP, the reduction in FVC decline was not significant at any of the time points analyzed. In conclusion, pirfenidone reduces FVC decline in IPF patients. However, its beneficial effect is more pronounced in patients with rapidly progressive disease.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by progressive loss of lung function and poor prognosis. The so-called acute exacerbation of IPF (AE-IPF) may lead to severe hypoxemia requiring mechanical ventilation in the intensive care unit (ICU). AE-IPF shares several pathophysiological features with acute respiratory distress syndrome (ARDS), a very severe condition commonly treated in this setting. A review of the literature has been conducted to underline similarities and differences in the management of patients with AE-IPF and ARDS. During AE-IPF, diffuse alveolar damage and massive loss of aeration occurs, similar to what is observed in patients with ARDS. Differently from ARDS, no studies have yet concluded on the optimal ventilatory strategy and management in AE-IPF patients admitted to the ICU. Notwithstanding, a protective ventilation strategy with low tidal volume and low driving pressure could be recommended similarly to ARDS. The beneficial effect of high levels of positive end-expiratory pressure and prone positioning has still to be elucidated in AE-IPF patients, as well as the precise role of other types of respiratory assistance (e.g., extracorporeal membrane oxygenation) or innovative therapies (e.g., polymyxin-B direct hemoperfusion). The use of systemic drugs such as steroids or immunosuppressive agents in AE-IPF is controversial and potentially associated with an increased risk of serious adverse reactions. Common pathophysiological abnormalities and similar clinical needs suggest translating to AE-IPF the lessons learned from the management of ARDS patients. Studies focused on specific therapeutic strategies during AE-IPF are warranted.

Best supportive care (BSC) is generally defined as all the interventions and the multiprofessional approach aimed to improve and optimise quality of life (QoL) in patients affected by progressive diseases. In this sense, it excludes and might be complementary to other interventions directly targeting the disease. BSC improves survival in patients with different types of cancer. Patients with idiopathic pulmonary fibrosis (IPF) experience a vast range of symptoms during the natural history of the disease and might have a beneficial effect of BSC interventions. This review highlights the current evidence on interventions targeting QoL and gaps for the clinical assessment of BSC in the treatment of IPF patients. Very few interventions to improve QoL or improve symptom control are currently supported by well-designed studies. Sound methodology is paramount in evaluating BSC in IPF, as well as the use of validated tools to measure QoL and symptom control in this specific group of patients.

There are over 200 interstitial lung diseases (ILDs). In addition to patients with idiopathic pulmonary fibrosis (IPF), a percentage of patients with other ILDs also develop progressive fibrosis of the lung during their disease course. Patients with progressive-fibrosing ILDs may show limited response to immunomodulatory therapy, worsening symptoms and lung function and, ultimately, early mortality. There are few data for ILDs that may present a progressive fibrosing phenotype specifically, but we believe the burden and healthcare costs associated with these conditions may be comparable to those reported in IPF. This review discusses the burden of ILDs that may present a progressive fibrosing phenotype and the factors impacting healthcare utilisation.

Background: Two therapeutic options are currently available for patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. To date, there is still insufficient data on the efficacy of these 2 agents in patients with more severe disease. Objectives: This national, multicenter, retrospective real-life study was intended to determine the impact of nintedanib on the treatment of patients with severe IPF. Methods: All patients included had severe IPF and had to have at least 6 months of follow-up before and at least 6 months of follow-up after starting nintedanib. The aim of the study was to compare the decline in lung function before and after treatment. Patient survival after 6 months of therapy with nintedanib was assessed. Results: Forty-one patients with a forced vital capacity (FVC) ≤50% and/or a diffusing capacity of the lung for carbon monoxide (DLCO) ≤35% predicted at the start of nintedanib treatment were enrolled. At the 6-month follow-up, the decline of DLCO (both absolute and % predicted) was significantly reduced compared to the pretreatment period (absolute DLCO at the -6-month, T0, and +6-month time points (5.48, 4.50, and 5.03 mmol/min/kPa, respectively, p = 0.03; DLCO% predicted was 32.73, 26.54, and 29.23%, respectively, p = 0.04). No significant beneficial effect was observed in the other functional parameters analyzed. The 1-year survival in this population was 79%, calculated from month 6 of therapy with nintedanib. Conclusions: This nationwide multicenter experience in patients with severe IPF shows that nintedanib slows down the rate of decline of absolute and % predicted DLCO but does not have significant impact on FVC or other lung parameters.

Objectives: To apply the Delphi exercise with iterative involvement of radiologists and pulmonologists with the aim of defining a structured reporting template for high-resolution computed tomography (HRCT) of patients with fibrosing lung disease (FLD). Methods: The writing committee selected the HRCT criteria—the Delphi items—for rating from both radiology panelists (RP) and pulmonology panelists (PP). The Delphi items were first rated by RPs as “essential”, “optional”, or “not relevant”. The items rated “essential” by < 80% of the RP were selected for the PP rating. The format of reporting was rated by both RP and PP. Results: A total of 42 RPs and 12 PPs participated to the survey. In both Delphi round 1 and 2, 10/27 (37.7%) items were rated “essential” by more than 80% of RP. The remaining 17/27 (63.3%) items were rated by the PP in round 3, with 2/17 items (11.7%) rated “essential” by the PP. PP proposed additional items for conclusion domain, which were rated by RPs in the fourth round. Poor consensus was observed for the format of reporting. Conclusions: This study provides a template for structured report of FLD that features essential items as agreed by expert thoracic radiologists and pulmonologists

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and inevitably fatal lung disease. Although the etiology and pathogenesis of IPF remain incompletely understood, two drugs (e.g., pirfenidone and nintedanib) have proven effective in slowing down functional decline and disease progression and are now approved worldwide for treatment. Yet, as outlined by the recent guideline document on treatment of IPF, every therapeutic decision needs to be tailored to the individual patient, after discussing potential benefits and pitfalls. Comorbidities, which almost invariably complicate IPF, impact significantly clinical course and prognosis of the disease, making a holistic approach to the best care for these patients. Randomized-controlled trials remain a valid choice for selected IPF patients and their completion is critically important to achieving the ultimate goal of improving both survival and quality of life of patients suffering from this devastating disease.

The diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis is fundamental to improving their survival rate. In particular, the average survival time of patients affected by rheumatoid arthritis with pulmonary implications is approximately 3 years. The gold standard for confirming the diagnosis of this disease is computer tomography. However, it is very difficult to raise diagnosis suspicion because the symptoms of the disease are extremely common in elderly people. The detection of the so-called velcro crackle in lung sounds can effectively raise the suspicion of an interstitial disease and speed up diagnosis. However, this task largely relies on the experience of physicians and has not yet been standardized in clinical practice. The diagnosis of interstitial lung diseases based on thorax auscultation still represents an underexplored field in the study of rheumatoid arthritis. In this study, we investigate the problem of the automatic detection of velcro crackle in lung sounds. In practice, the patient is auscultated using a digital stethoscope and the lung sounds are saved to a file. The acquired digital data are then analysed using a suitably developed algorithm. In particular, the proposed solution relies on the empirical observation that the audio bandwidth associated with velcro crackle is larger than that associated with healthy breath sounds. Experimental results from a database of 70 patients affected by rheumatoid arthritis demonstrate that the developed tool can outperform specialized physicians in terms of diagnosing pulmonary disorders. The overall accuracy of the proposed solution is 90.0%, with negative and positive predictive values of 95.0% and 83.3%, respectively, whereas the reliability of physician diagnosis is in the range of 60−70%. The devised algorithm represents an enabling technology for a novel approach to the diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis.

Background: Systemic sclerosis (SSc) is an autoimmune systemic disease characterized by diffuse fibrosis of skin and visceral organs due to different genetic, infectious, and/or environmental/occupational causative factors, including the inhalation of silica dust. Objectives: To investigate serum trace elements including silicon (s-Si) levels in SSc patients living in a restricted geographical area with high density of worksites with silica exposure hazard. Methods: This case-control study included 80 SSc patients (M:F 10:70; aged 58.4 ± 11.9SD years, mean disease duration 10.1 ± 7.8SD) and 50 age-/sex-matched healthy control subjects consecutively investigated at our University-based Rheumatology Unit. Patients and controls were evaluated for environmental/occupational exposure categories (structured questionnaire), morphological characterization of serum micro-/nanoparticles (Environmental Scanning Electron Microscopy and Energy Dispersive X-ray Spectroscopy microanalysis), and quantitative assessment of trace elements (inductively coupled plasma atomic emission spectroscopy). Results: Among various categories, only occupational exposure to silica dust was recorded in a significant proportion of SSc patients compared to controls (55% vs. 11%; p <.0001). Qualitative analysis showed serum silica micro- and nanoparticles in all exposed patients. Quantitative evaluation evidenced significantly higher s-Si levels in SSc patients versus controls (p <.0001); in addition, higher s-Si levels were detected in patients with occupational exposure (p <.0001), diffuse cutaneous SSc (p =.0047), myositis (p =.0304), and/or lung fibrosis (p =.0004) compared to those without; notably, the severity of lung fibrosis scoring positively correlated with s-Si levels (p <.0001). Conclusions: The study first demonstrated high s-Si levels in exposed SSc patients; this element might represent a pathogenetic co-factor of more severe clinical phenotypes, mainly diffuse scleroderma with lung fi

BACKGROUND Recent studies have suggested a decline in subjective well-being after the birth of a first child. Yet parents' subjective well-being is, in general, linked positively to wanting and to having additional children. OBJECTIVE The paper addresses the question of whether new parents' satisfaction with their overall life and several specific life spheres modifies their expectations about having a second, or further, child. METHODS Relying on twelve waves of the Household, Income and Labour Dynamics in Australia panel survey (2001-2012), we apply piecewise growth models to a sample of individuals in couples who experience parenthood for the first time. We model, separately by gender, the relationship between satisfaction in seventeen life domains, overall life satisfaction, and fertility expectations during the first three years following the birth of a first child. RESULTS Results suggest that a decline in new parents' life satisfaction, overall and in different life domains, is associated with a significant decline in fertility expectations. The most important domains are family, social relationship, and work, although with differences by gender. In fact, mothers' fertility expectations are positively associated with their satisfaction with career prospects and with their work-family balance, whereas, for fathers, fertility expectations are positively associated with their financial situation. CONTRIBUTION Our study provides strong evidence that several life domains - and new parents' changes in satisfaction with regard to them - are important in elucidating the mechanism linking fertility expectations and the first child.

Impaired diffusing capacity of the lung for carbon monoxide (DLCO) was frequently observed in systemic sclerosis (SSc) patients, generally related to the presence of interstitial lung disease (ILD) and/or pulmonary arterial hypertension (PAH). However, in clinical practice abnormally low DLCO values may be found also in the absence of these SSc complications. The objective was to investigate the prospective clinical relevance of isolated DLCO reduction at baseline in SSc patients. Ninety-seven SSc female patients (age at the diagnosis: 51.3±14.5 years; disease duration: 10.4±6.6 years; limited/diffuse skin subsets: 92/5), without any clinical, radiological (high resolution computed tomography), and echocardiographic manifestations of ILD or PAH at baseline, nor other lung or heart diseases able to affect DLCO, were recruited at our Rheumatology Centre. Patients with DLCO <55% (15 patients; group A) were compared with those with normal DLCO (82 patients; group B), at baseline and at the end of follow-up. At baseline, patients of group A showed significantly higher percentage of anticentromere autoantibodies compared to group B (13/15, 86.6% vs 48/82, 58.5%; p=0.044). More interestingly, at the end of long-lasting clinical follow-up (11.6±6.7 years), pre-capillary PAH (right heart catheterization) solely developed in some patients of group A (3/15, 20% vs 0/82; p=0.003). In SSc patients, the presence at baseline of isolated, marked DLCO reduction (<55% of predicted) and serum anticentromere autoantibodies might characterize a peculiar SSc subset that may precede the development of PAH. Therefore, careful clinical follow-up of patients with isolated moderate-severe DLCO reduction should be mandatory.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic disease limited to the lung, with high variability in the course of disease from one patient to another. Patients with IPF may experience acute respiratory deteriorations; many of these acute declines are idiopathic and are termed acute exacerbations (AE) of IPF. In these cases, the exclusion of alternative causes of rapid deterioration, including heart failure, bilateral pneumonia or pulmonary embolism, is a challenging goal. AE may occur at any time during the course of IPF, although they are more common in patients with more progressive disease and gastroesophageal reflux. Surgical lung biopsy or even surgical procedures in organs other than the lungs may also trigger AE, mainly in rapidly progressive or advanced IPF. Current diagnostic criteria include the presence of new-onset ground glass opacities or airspace consolidation superimposed on an underlying usual interstitial pneumonia pattern seen on high-resolution computed tomography. The outcome is poor with a short-term mortality in excess of 50 % despite therapy. Currently, there is no treatment with demonstrated efficacy for AE-IPF: empirical high-dose corticosteroid therapy is generally used, with or without immunosuppressive agents, with limited evidence. On the other hand, there is hope that new treatments to slow down progression of IPF will translate into a reduction of AE-IPF’s occurrence. In conclusion, although significant progress in assessing disease severity in IPF has been made, AEs remain unpredictable and are associated with a high risk of death. Improvements in our understanding of the etiology, risk factors, clinical predictors and epidemiology are needed. It is the goal of clinical researchers in the field to provide respiratory physicians with evidence-based guidance to identify patients who may benefit from therapy for preventing or treating AE-IPF.

We investigated the clinical performance of a polymerase chain reaction (PCR)-based commercial platform, the Myconostica MycAssayTM Aspergillus (MAP), for fungal DNA detection in the serum of patients at risk of invasive aspergillosis (IA). Sixty-four hospitalized patients were prospectively enrolled and a total of 71 different episodes were investigated (30 episodes were clinically/microbiologically classified as IA and 41 as control episodes). When MAP was compared to the galactomannan (GM) assay, no significant differences were found in terms of sensitivity (46.7 % vs. 50.0 %), specificity (97.6 % vs. 95.1 %), positive predictive value (PPV) (93.3 % vs. 88.2 %), and negative predictive value (NPV) (71.4 % vs. 72.2 %). The corresponding areas under the curve (AUC) of the receiver operating characteristic (ROC) curves were also superimposable. Overall, because of the good agreement between the two assays and considering the high specificity and PPV of the MAP, we suggest the use of this PCR-based platform as a second-level examination for the evaluation of clinically undefined cases where culture or GM have provided positive results.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial joint swelling and tenderness, secondary to the immune-system dysfunction, often complicated by extra-articular manifestations. Among them, lung involvement is very frequent and interstitial lung disease (ILD) represents one of the deleterious complications of RA with impact on both therapeutic approach and overall prognosis. Nevertheless, diagnosis of ILD often remains missing or delayed. Objectives: To preliminarily evaluate the predictive value of pulmonary sound recorded by an electronic stethoscope (ES) and elaborated by an ad hoc software in identification of RA-ILD diagnosed by mean of high resolution computed tomography (HRCT) in a multicenter study. Methods: RA patients who underwent HRCT in the last 12 months were enrolled. They were all auscultated with the ES (Littmann 3200TM 3M, USA), bilaterally, at dorsal level, in at least 3 pulmonary fields (medium and basal). All tracks recorded were analyzed by a suitably developed software capable of recognizing pathological crackles in lung sounds. Results were compared with radiologic findings detected in a blind manner by an expert radiologist. Results: One hundred and six RA patients were enrolled (M/F: 1/2.5, mean age 68.7±10.3); among them 45 (42.5%) showed ILD at HRCT. Three patients were excluded because of a low quality of the sound recorded. The algorithm showed a sensitivity and specificity of 72.1% and 84.4%, respectively and a positive/negative predictive value of 69.1% and 86.3%, respectively. Conclusions: Despite preliminary, these data suggest an important role of ES in clinical practice for an early diagnosis of ILD in RA patients and a significant reduction of inappropriate prescription of HRCT. Since very different types of ILD can occur in course of RA, with different radiologic features and localization, proper development of the measurement setup (ES and ad hoc software for the detection of PC)

Background: Recent evidences show that Pulmonary Rehabilitation (PR) is effective in patients with Interstitial Lung Disease (ILD). It is still unclear whether disease severity and/or etiology might impact on the reported benefits. We designed this prospective study 1) to confirm the efficacy of rehabilitation in a population of patients with ILDs and 2) to investigate whether baseline exercise capacity, disease severity or ILD etiology might affect outcomes. Methods: Forty-one patients (IPF 63%, age 66.9 ± 11 ys) were enrolled in a standard PR course in two centers. Lung function, incremental and endurance cyclo-ergometry, Six Minutes Walking Distance (6MWD), chronic dyspnea (Medical Research Council scale-MRC) and quality of life (St. George Respiratory Questionnaire-SGRQ) were recorded before and at the end of PR to measure any pre-to-post change. Correlation coefficients between the baseline level of Diffuse Lung Capacity for Carbon monoxide (DLCO), Forced Vital Capacity (FVC), 6MWD, power developed during incremental endurance test, GAP index (in IPF patients only) and etiology (IPF or non-IPF) with the functional improvement at the 6MWDT (meters), at the incremental and endurance cyclo-ergometry (endurance time) and the HRQoL were assessed. Results: Out of the 41 patients, 97% (n = 40) completed the PR course. Exercise performance (both at peak load and submaximal effort), symptoms (iso-time dyspnea and leg fatigue), SGRQ and MRC significantly improved after PR (p < .001). Patients with lower baseline 6MWD showed greater improvement in 6MWD (Spearman r score = -.359, p = .034) and symptoms relief at SGRQ (r = -.315, p = .025) regardless of underlying disease. Conclusion: Present study confirms that comprehensive rehabilitation is feasible and effective in patients with ILD of different severity and etiology. The baseline submaximal exercise capacity inversely correlates with both functional and symptom gains in this heterogeneous population.

This article originally published with all author names incorrectly listed. All author names have now been transposed and appear correctly above. The original article was corrected.

Le pneumopatie infiltative diffuse (PID) o interstiziopatie polmonari rappresentano un ampio ed eterogeneo gruppo di patologie, alcune a esclusivo interessamento polmonare, altre in cui il polmone è solo uno degli organi colpiti. Le PID possono insorgere in modo acuto, subacuto o cronico, o avere un decorso subclinico e indolente. Inoltre, mentre alcune di esse possono regredire (con o senza terapia), altre, quali la fibrosi polmonare idiopatica, progrediscono in modo inesorabile, anche se alcuni farmaci ad azione antifibrotica sono in grado di rallentarne la progressione.

Primary Sjögren syndrome (pSS)-related interstitial lung disease (ILD) involved about 10–20% of patients. In 20% of cases, ILD can be diagnosed before pSS; anyway, few studies have investigated the frequency of ILD as the first clinically relevant manifestation of pSS, generally referred to retrospective studies. Aim of our prospective study was to describe prevalence, clinical, serological, and instrumental features of non-sicca onset pSS patients with interstitial lung involvement. During a period of 48 months, all consecutive patients diagnosed as pSS were enrolled. For all patients, the reason for the first visit was recorded. When present, ILD was categorized as definite, possible, or inconsistent with usual interstitial pneumonia (UIP) pattern, according to the current criteria. ILD was the main presenting symptom in 13/77 new diagnoses of pSS patients; in particular, 6/13 patients were initially diagnosed as idiopathic ILD, and only later developed clinical manifestations suggestive for pSS; ILD-pSS patients were older than others and showed a higher EULAR primary Sjögren’s syndrome disease activity index. A radiologic definite or possible UIP pattern was detected in 12/13 pSS. For the first time, we prospectively observed a prevalence of 16.8% of non-sicca onset pSS patients with ILD. Interestingly, UIP pattern was the most frequently detected, while typical autoantibodies were often absent. These features stressed the importance of differential diagnosis in the first stage of the disease, considering the possible poorer prognosis in this subgroup of patients. Multidisciplinary approach is crucial for a correct and early diagnosis, at both onset and follow-up.

Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of complex cause. Gastro-oesophageal reflux (GER) and microaspiration have been proposed as risk factors for the development and progression of IPF, but robust definitive data are few. A recent international guideline conditionally recommended the use of antacid therapy (proton pump inhibitors or histamine-2-receptor antagonists) for patients with IPF, in the absence of oesophageal reflux or symptoms. In this Position Paper, we summarise the literature addressing the association between GER and IPF, and also identify future research priorities that could clarify this issue. We shed light on the process through which the guideline recommendation was achieved and aim to contextualise the recommendation for providers caring for patients with IPF.