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Many data already suggested that cancer and IPF are underlined by a number of common pathogenic biologic pathways. However, fewer data regards the interconnections, in terms of synergy or increased toxicities, of drugs used in cancer and IPF. Particularly, how the specific therapy influences the concurrent condition and prognostic factors of response in patients with both lung cancer and IPF are far to be clarified. Similarly, identification of features of IPF patients with higher risk of developing pulmonary adverse events when treated with chemotherapy, immune checkpoint inhibitors, TKIs, or radiotherapy is of primary importance in clinical practice.We will discuss the scientific rationale, based on the extensive analysis of literature data, by consulting several databases for combining anticancer and antifibrotic treatments and for the design of novel therapeutic strategies. The role of immunotherapy in cancer aroused in IPF context will be discussed with specific interested, based on the continuously increasing role of immune checkpoint inhibition against lung tumors.This work will help to improve knowledge, based on a multidisciplinary perspective, on IPF and cancer patients, which identify an unmet clinical need. A better management during each phase of disease progression will require the design innovative trials and the development of new drugs and molecules both in the oncologic and respiratory medicine pipeline.

The present report investigates the impact of a Telemedicine Service (TMS) on the management of Idiopathic Pulmonary Fibrosis (IPF) during coronavirus disease of 2019 (COVID-19) outbreak in Italy. The TMS comprised 3 phone numbers, active 12 h per day, and an email address, monitored every 4 h by trained physicians; chat- and videoconference-services were also offered. At the end of the study period, our staff contacted all patients, to get information about the final outcome (i.e. composite hospitalisations/all causes of death). Outcomes were compared with a cohort of patients who attended our unit in the same period of the previous year (when no TMS was available). 189 patients participated in the present study. From 11th March to 4th May 2020, 61% of patients made at least one TMS access, mostly by emails (53%), followed by phone calls (33%). With regard to the primary outcome, TMS patients experienced a significant lower rate of events of the 182 patients of the no-TMS cohort (p < 0.001). Specifically, a significant difference was observed for IPF hospitalisation (p < 0.001) whereas no differences were observed with regard to deaths (p = 0.64). TMS permits patients to be followed up even during COVID-19 lockdown, with an encouraging impact on outcomes.

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.

Background Volumetric high-resolution computed tomography (HRCT) of the chest has recently replaced incremental CT in the diagnostic workup of idiopathic pulmonary fibrosis (IPF). Concomitantly, visual and quantitative scores have been proposed for disease extent assessment to ameliorate disease management. Purpose To compare the performance of density histograms (mean lung attenuation, skewness, and kurtosis) and visual scores, along with lung function correlations, in IPF patients submitted to incremental or volumetric thorax HRCT. Material and methods Clinical data and CT scans of 89 newly diagnosed and therapy-naive IPF patients were retrospectively evaluated. Results Forty-six incremental and 43 volumetric CT scans were reviewed. No differences of density histograms and visual scores estimates were found by comparing two HRCT techniques, with an optimal inter-operator agreement (concordance correlation coefficient >0.90 in all instances). Single-breath diffusing lung capacity for carbon monoxide (DLCOsb) was inversely related with the Best score (r = −00.416; p = 0.014), the Kazerooni fibrosis extent (r = −0.481; p = 0.004) and the mean lung attenuation (r = −0.382; p = 0.026), while a positive correlation was observed with skewness (r = 0.583; p = 0.001) and kurtosis (r = 0.543; p = 0.001) in the incremental HRCT sub-group. Similarly, in the volumetric CT sub-cohort, DLCOsb was significantly associated with skewness (r = 0.581; p = 0.007) and kurtosis (r = 0.549; p = 0.018). Correlations with visual scores were not confirmed. Forced vital capacity significantly related to all density indices independently on HRCT technique. Conclusions Density histograms and visual scores similarly perform in incremental and volumetric HRCT. Density quantification displays an optimal reproducibility and proves to be superior to visual scoring as more strongly correlated with lung function.

Idiopathic pulmonary fibrosis is a progressive disease, with a high mortality within the first 3-5 years from diagnosis and a poor quality of life mainly because of the burden of symptoms, such as dyspnea and cough, occurring usually many months before the diagnosis. Although available antifibrotic therapies slow down disease progression, they have no impact on quality of life. Moreover, health care around idiopathic pulmonary fibrosis patients is often "disease-centered" and relies on clinical surrogate outcomes that are poorly related to patients' quality of life and disease experience. Therefore, patients with idiopathic pulmonary fibrosis have several unmet needs in all domains of health that they wish to see recognized and addressed in the context of the treatment of their disease and its complications. In this review, we summarize the care pathway from the patients' perspective, identifying current gaps in care, education, support, and communication among patients with IPF, their caregivers, and care teams during the patient journey. The role of patient-reported outcomes (PROs), PRO measures (PROMs), and patient-reported experience measures (PREMs) in their care is discussed, as well as the need of disease-specific PROs, PROMs, and PREMs.

The aim of the study was to evaluate the trend in the incidence of idiopathic pulmonary fibrosis (IPF) in a real-world setting of the Marche region, a region of Central Italy, between 2014 and 2019. This observational prospective study was based on administrative databases of hospital discharges and drug prescriptions. All adult residents in the Marche Region with a first prescription of antifibrotic drugs, or a first hospitalization with a diagnosis of IPF during the study period, were identified as incident cases of IPF. A multiple Poisson regression analysis was used to estimate the IPF incidence trend, adjusted for age, sex, and health conditions. The mean incidence rate was 9.8 cases per 100,000 person-years. A significant increasing trend of 6% per year was observed. The incidence rates were significantly higher in males than females, older subjects, and those with poorer health conditions. To our knowledge, this is the first study evaluating incidences of IPF over a 6-year period in Italy, combining hospital discharge and drug prescription databases. The study highlights that the combined use of two secondary sources is a reliable strategy to accurately identify new cases of IPF when the appropriate disease registry is lacking.

SummaryTherapies halting the progression of fibrosis are ineffective and limited. Activated myofibroblasts are emerging as important targets in the progression of fibrotic diseases. Previously, we performed a high-throughput screen on lung fibroblasts and subsequently demonstrated that the inhibition of myofibroblast activation is able to prevent lung fibrosis in bleomycin-treated mice. High-throughput screens are an ideal method of repurposing drugs, yet they contain an intrinsic limitation, which is the size of the library itself. Here, we exploited the data from our “wet” screen and used “dry” machine learning analysis to virtually screen millions of compounds, identifying novel anti-fibrotic hits which target myofibroblast differentiation, many of which were structurally related to dopamine. We synthesized and validated several compounds ex vivo (“wet”) and confirmed that both dopamine and its derivative TS1 are powerful inhibitors of myofibroblast activation. We further used RNAi-mediated knock-down and demonstrated that both molecules act through the dopamine receptor 3 and exert their anti-fibrotic effect by inhibiting the canonical transforming growth factor β pathway. Furthermore, molecular modelling confirmed the capability of TS1 to bind both human and mouse dopamine receptor 3. The anti-fibrotic effect on human cells was confirmed using primary fibroblasts from idiopathic pulmonary fibrosis patients. Finally, TS1 prevented and reversed disease progression in a murine model of lung fibrosis. Both our interdisciplinary approach and our novel compound TS1 are promising tools for understanding and combating lung fibrosis.

The aim was to evaluate the determinants of acute exacerbation (AE) and death in new cases of idiopathic pulmonary fibrosis (IPF) using administrative databases in the Marche Region. Adults at their first prescription of antifibrotics or hospitalization with a diagnosis of IPF occurring in 2014–2019 were considered as new cases. Multiple Cox regression was used to estimate the risk of AE and of all-cause mortality adjusted by demographic and clinical characteristics, stratifying patients according to antifibrotic treatment. Overall, 676 new cases of IPF were identified and 276 deaths and 248 AE events occurred. In never-treated patients, the risk of AE was higher in patients with poor health conditions at diagnosis; the risk of death was higher in males, in patients aged ≥75 and in those with poor health conditions at baseline. The increasing number of AEs increased the risk of death in treated and never-treated patients. Within the limits of an observational study based on secondary data, the combined use of healthcare administrative databases allows the accurate analysis of progression and survival of IPF from the beginning of the antifibrotic therapy era, suggesting that timely and early diagnosis is critical to prescribing the most suitable treatment to increase survival and maintain a healthy life expectancy.

Body composition and muscle strength are emerging aspects in idiopathic pulmonary fibrosis (IPF) clinical assessment. We aimed to study the relationships of handgrip strength (HGS) with anthropometric variables, body composition, and disease staging, and to evaluate the prevalence of dynapenia in 102 clinically stable IPF patients (70 M; mean age: 69.4 years). Fat-free mass (FFM), skeletal muscle (SM) were estimated with bioimpedance analysis. HGS was measured with a digital handle dynamometer for both dominant and non-dominant body sides. Dynapenia was identified according to six recognized criteria sets. Mean body mass index (BMI) was 28.2 ± 4.7 kg/m2, with a prevalence of overweight (BMI > 25 and 2) and obesity (BMI ≥ 30 kg/m2) of 35% and 37%, respectively. FFM and SM were greater in males, whereas percentage body fat was higher in women. HGS was higher and declined with age slightly more rapidly in men, showing a stronger correlation with FFM and SM. Dynapenia prevalence ranged from 20.6 to 56.9%, depending on the criteria used, and was more frequent in older patients and advanced disease. Dynapenia is highly prevalent in IPF. HGS is a promising proxy marker of muscle function to be used in clinical evaluation and follow-up programs.

Interstitial lung diseases (ILDs) comprise a wide group of pulmonary parenchymal disorders. These patients may experience acute respiratory deteriorations of their respiratory condition, termed “acute exacerbation” (AE). The incidence of AE-ILD seems to be lower than idiopathic pulmonary fibrosis (IPF), but prognosis and prognostic factors are largely unrecognized. We retrospectively analyzed a cohort of 158 consecutive adult patients hospitalized for AE-ILD in two Italian university hospitals from 2009 to 2016. Patients included in the analysis were divided into two groups: non-IPF (62%) and IPF (38%). Among ILDs included in the non-IPF group, the most frequent diagnoses were non-specific interstitial pneumonia (NSIP) (42%) and connective tissue disease (CTD)-ILD (20%). Mortality during hospitalization was significantly different between the two groups: 19% in the non-IPF group and 43% in the IPF group. AEs of ILDs are difficult-to-predict events and are burdened by relevant mortality. Increased inflammatory markers, such as neutrophilia on the differential blood cell count (HR 1.02 (CI 1.01–1.04)), the presence of pulmonary hypertension (HR 1.85 (CI 1.17–2.92)), and the diagnosis of IPF (HR 2.31 (CI 1.55–3.46)), resulted in negative prognostic factors in our analysis. Otherwise, lymphocytosis on the differential count seemed to act as a protective prognostic factor (OR 0.938 (CI 0.884–0.995)). Further prospective, large-scale, real-world data are needed to support and confirm the impact of our findings.

Idiopathic pulmonary fibrosis (IPF), the most lethal form of interstitial pneumonia of unknown cause, is associated with a specific radiological and histopathological pattern (the so-called “usual interstitial pneumonia” pattern) and has a median survival estimated to be between 3 and 5 years after diagnosis. However, evidence shows that IPF has different clinical phenotypes, which are characterized by a variable disease course over time. At present, the natural history of IPF is unpredictable for individual patients, although some genetic factors and circulating biomarkers have been associated with different prognoses. Since in its early stages, IPF may be asymptomatic, leading to a delayed diagnosis. Two drugs, pirfenidone and nintedanib, have been shown to modify the disease course by slowing down the decline in lung function. It is also known that 5–10% of the IPF patients may be affected by episodes of acute and often fatal decline. The acute worsening of disease is sometimes attributed to identifiable conditions, such as pneumonia or heart failure; but many of these events occur without an identifiable cause. These idiopathic acute worsenings are termed acute exacerbations of IPF. To date, clinical biomarkers, diagnostic, prognostic, and theranostic, are not well characterized. However, they could become useful tools helping facilitate diagnoses, monitoring disease progression and treatment efficacy. The aim of this review is to cover molecular mechanisms underlying IPF and research into new clinical biomarkers, to be utilized in diagnosis and prognosis, even in patients treated with antifibrotic drugs.

Galectins are ten family members of carbohydrate-binding proteins with a high affinity for β galactose-containing oligosaccharides. Galectin-1 (Gal-1) is the first protein discovered in the family, expressed in many sites under normal and pathological conditions. In the first part of the review article, we described recent advances in the Gal-1 modulatory role on wound healing, by focusing on the different phases triggered by Gal-1, such as inflammation, proliferation, tissue repair and re-epithelialization. On the contrary, Gal-1 persistent over-expression enhances angiogenesis and extracellular matrix (ECM) production via PI3K/Akt pathway activation and leads to keloid tissue. Therefore, the targeted Gal-1 modulation should be considered a method of choice to treat wound healing and avoid keloid formation. In the second part of the review article, we discuss studies clarifying the role of Gal-1 in the pathogenesis of proliferative diabetic retinopathy, liver, renal, pancreatic and pulmonary fibrosis. This evidence suggests that Gal-1 may become a biomarker for the diagnosis and prognosis of tissue fibrosis and a promising molecular target for the development of new and original therapeutic tools to treat fibrosis in different chronic diseases.

Idiopathic pulmonary fibrosis (IPF) is the most devastating progressive interstitial lung disease that remains refractory to treatment. Pathogenesis of IPF relies on the aberrant cross-talk between injured alveolar cells and myofibroblasts, which ultimately leads to an aberrant fibrous reaction. The contribution of the immune system to IPF remains not fully explored. Recent evidence suggests that both innate and adaptive immune responses may participate in the fibrotic process. Dendritic cells (DCs) are the most potent professional antigen-presenting cells that bridge innate and adaptive immunity. Also, they exert a crucial role in the immune surveillance of the lung, where they are strategically placed in the airway epithelium and interstitium. Immature DCs accumulate in the IPF lung close to areas of epithelial hyperplasia and fibrosis. Conversely, mature DCs are concentrated in well-organized lymphoid follicles along with T and B cells and bronchoalveolar lavage of IPF patients. We have recently shown that all sub-types of peripheral blood DCs (including conventional and plasmacytoid DCs) are severely depleted in therapy naïve IPF patients. Also, the low frequency of conventional CD1c+DCs is predictive of a worse prognosis. The purpose of this mini-review is to focus on the main evidence on DC involvement in IPF pathogenesis. Unanswered questions and opportunities for future research ranging from a better understanding of their contribution to diagnosis and prognosis to personalized DC-based therapies will be explored.

Background. Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD). This prospective observational study aimed at the evaluation of any correlation between genetic variants associated with IPF susceptibility and high-resolution computed tomography (HRCT) patterns. It also aimed at evidencing any differences in the HRTC pattern between the familial and sporadic form at diagnosis and after two years. Methods. A total of 65 IPF patients (mean age at diagnosis 65 ± 10) were enrolled after having given written informed consent. HRCT and genetic evaluations were performed. Results. A total of 19 familial (mean age 62 ± 15) and 46 sporadic (mean age 70 ± 9) IPF patients were enrolled. A statistically significant difference was evidenced in the HRTC pattern at diagnosis between the two groups. Sporadic IPF patients had a predominantly usual interstitial pneumonia (UIP) pattern compared with those patients with familial IPF (60.0% vs. 21.1%, respectively). Moreover, familial IPF patients had more alternative diagnoses than those with sporadic IPF (31.6% vs. 2.2%, respectively). Furthermore, there was a slight increase in the typical UIP pattern in the familial IPF group at two years from diagnosis. Conclusions. Genetic factors play a pivotal role in the risk of developing IPF. However, further studies are required to clarify how these genetic factors may guide clinical treatment decisions.

Anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (MPO) antibodies, have been frequently identified in patients with idiopathic pulmonary fibrosis (IPF). However, their role remains unclear, and only 7–23% of these patients develops clinically overt vasculitis. We aimed to investigate the clinical, serological, and radiological features and prognosis of anti-MPO-positive interstitial lung disease (ILD) patients. Fifty-eight consecutive patients firstly referred for idiopathic interstitial pneumonia and showing serological positivity of anti-MPO antibodies were retrospectively enrolled. For each patient, clinical data, lung function testing, chest high-resolution computed tomography (HRCT) pattern, and survival were recorded. Thirteen patients developed a rheumatic disease during a median follow-up of 39 months. Usual interstitial pneumonia (UIP) was the most frequent ILD pattern, significantly influencing the patients’ survival. In fact, while the 52-week survival of the overall population was 71.4 ± 7.5%, significantly higher than IPF, survivals of anti-MPO patients with UIP pattern and IPF were similar. Forced vital capacity and diffusion lung capacity for CO significantly declined in 37.7 and 41.5% of cases, respectively, while disease progression at chest HRCT was observed in 45.2%. A careful clinical history and evaluation should always be performed in ILD patients with anti-MPO antibodies to quickly identify patients who are developing a systemic rheumatic disease.

Ο σκοπός της παρούσας διδακτορικής διατριβής ήταν η διερεύνηση των αιτιολογικών και προγνωστικών παραγόντων που σχετίζονται με δύο χρόνια πνευμονολογικά νοσήματα που έχουν αξιοσημείωτη νοσηρότητα και θνητότητα, την χρόνια αποφρακτική πνευμονοπάθεια (ΧΑΠ) και την ιδιοπαθή πνευμονική ίνωση (ΙΠΙ). Ο πρώτος στόχος της διδακτορικής διατριβής ήταν η κριτική αποτίμηση της επιδημιολογικής αξιοπιστίας των παραγόντων κινδύνου της ΧΑΠ. Για το σκοπό αυτό πραγματοποιήθηκε μία ανασκόπηση πεδίου τύπου ομπρέλας. Έγινε αρχικά συστηματική αναζήτηση για να ανευρεθούν συστηματικές ανασκοπήσεις και μετα-αναλύσεις μελετών παρατήρησης που εξετάζουν την συσχέτιση περιβαλλοντικών παραγόντων και βιοδεικτών με τον κίνδυνο για ΧΑΠ. Στην συνέχεια εφαρμόστηκαν ορισμένα τυποποιημένα μεθοδολογικά κριτήρια βάσει του επιπέδου στατιστικής σημαντικότητας, του μεγέθους δείγματος, της ετερογένειας μεταξύ των μελετών και των στατιστικών σφαλμάτων. Η αναζήτηση οδήγησε σε 11 άρθρα που πληρούσαν τα κριτήρια ένταξης, τα οποία περιλάμβαναν 18 μετα-αναλύσεις, και 8 άρθρα που περιείχαν μόνο συστηματική ανασκόπηση. Έντεκα συσχετίσεις ήταν στατιστικά σημαντικές με P-value 50%, ενώ έξι συσχετίσεις εμφάνισαν σφάλμα επίδρασης μικρών μελετών ή/ και σφάλμα περίσσειας στατιστικής σημαντικότητας. Το ιστορικό φυματίωσης ή ρευματοειδούς αρθρίτιδας, η έκθεση σε καύσιμα βιομάζας, το ενεργητικό κάπνισμα και το παθητικό κάπνισμα είχαν τεκμήρια με υψηλή επιδημιολογική αξιοπιστία για αυξημένο κίνδυνο για ΧΑΠ. Επίσης, ισχυρά ενδεικτικά τεκμήρια διαπιστώθηκαν για τα αυξημένα επίπεδα της C αντιδρώσας πρωτεΐνης και του ινωδογόνου στον ορό σε ασθενείς με ΧΑΠ σε σύγκριση με τους μάρτυρες. Συμπερασματικά, η προσέγγιση αυτή ανέδειξε ότι, παρόλο που ένα αξιοσημείωτο ποσοστό ασθενών με ΧΑΠ είναι μη καπνιστές, μόνο ένα περιορισμένο εύρος παραγόντων κινδύνου που δεν σχετίζονται με το κάπνισμα έχουν εξεταστεί ως παράγοντες κινδύνου της ΧΑΠ. Υπάρχει ανάγκη για περαιτέρω αποκωδικοποίηση των πιθανών προστατευτικών παραγόντων στην παθογένεση της ΧΑΠ δεδομένου ότι λιγότεροι από τους μισούς καπνιστές αναπτύσσουν ΧΑΠ. Ο δεύτερος στόχος της διδακτορικής διατριβής ήταν η χαρτογράφηση και η αξιολόγηση των προγνωστικών μοντέλων για κλινικές εκβάσεις σε ασθενείς με ΧΑΠ. Για το σκοπό αυτό έγινε συστηματική ανασκόπηση της βιβλιογραφίας μέσω αναζήτησης στην βάση δεδομένων PubMed και, έπειτα, έλεγχος των βιβλιογραφικών αναφορών των άρθρων που πληρούσαν τα κριτήρια ένταξης στην ανασκόπηση. Τα άρθρα που ήταν κατάλληλα για να επιλεγούν έπρεπε να περιγράφουν την ανάπτυξη, την επικύρωση ή την αναθεώρηση ενός προγνωστικού άρθρου σε ασθενείς με ΧΑΠ, εστιάζοντας σε οποιαδήποτε κλινική έκβαση. Η συστηματική αναζήτηση οδήγησε σε 228 άρθρα, τα οποία παρουσίασαν την ανάπτυξη 408 προγνωστικών μοντέλων, την εξωτερική επικύρωση 38 μοντέλων και την επικύρωση 20 προγνωστικών μοντέλων που αναπτύχθηκαν αρχικά για νοσήματα πέραν της ΧΑΠ. Τα 408 προγνωστικά μοντέλα αναπτύχθηκαν σε τρεις διακριτούς πληθυσμούς ασθενών: μη νοσηλευόμενους ασθενείς (239 προγνωστικά μοντέλα, 59%), νοσηλευόμενους ασθενείς (155 προγνωστικά μοντέλα, 38%) και ασθενείς που εξετάστηκαν στο τμήμα επειγόντων περιστατικών (14 προγνωστικά μοντέλα, 3%). Για τα 408 προγνωστικά μοντέλα, οι πιο συχνές εκβάσεις ήταν η θνητότητα (209 προγνωστικά μοντέλα, 51%), η οξεία παρόξυνση της νόσου (42 προγνωστικά μοντέλα, 10%) και η επανεισαγωγή μετά από μία νοσηλεία (36 μοντέλα, 9%). Συνολικά, οι πιο χρησιμοποιούμενοι προγνωστικοί παράγοντες ήταν η ηλικία (166 μοντέλα, 41%), ο βίαια εκπνεόμενος όγκος το 1ο δευτερόλεπτο (85 μοντέλα, 21%), το φύλο (74 μοντέλα, 18%), ο δείκτης μάζας σώματος (66 μοντέλα, 16%) και το κάπνισμα (65 μοντέλα, 16%). Η διακριτική ικανότητα του μοντέλου εκτιμήθηκε με το στατιστικό C για 311 (76%) μοντέλα, ενώ σε 91 (23%) μοντέλα εξετάστηκε η βαθμονόμηση. Από τα 408 προγνωστικά μοντέλα, 100 (25%) μοντέλα είχαν εσωτερική επικύρωση. Για 286 (70%) μοντέλα δεν υπήρχε κάποιος τρόπος παρουσίασης, και μόνο σε 56 (14%) ήταν διαθέσιμη η πλήρης εξίσωση. 38 μοντέλα επικυρώθηκαν σε ανεξάρτητο πληθυσμό, αλλά η επικύρωση έγινε από ανεξάρτητη ερευνητική ομάδα σε μόλις 12 από αυτά. Μόλις εφτά προγνωστικά μοντέλα είχαν χαμηλό κίνδυνο σφάλματος βάσει του εργαλείου PROBAST. Τα μοντέλα αυτά ήταν τα εξής: ADO, B-AE-D, B-AE-D-C, extended ADO, updated ADO, updated BODE και το μοντέλο από την ερευνητική ομάδα του Bertens. Πραγματοποιήθηκε μετα-ανάλυση του στατιστικού C για 12 προγνωστικά μοντέλα, και οι αθροιστικοί εκτιμητές κυμάνθηκαν από 0.611 έως 0.769. Τα ευρήματα της ανασκόπησης ανέδειξαν αρκετά μεθοδολογικά σφάλματα στην ανάπτυξη των μοντέλων και χαμηλό ποσοστό εξωτερικής επικύρωσης. Οι μελλοντικές ερευνητικές προσπάθειες πρέπει να εστιάσουν στην βελτίωση των υπαρχόντων μοντέλων, μέσω αναθεώρησης και εξωτερικής επικύρωσής τους, καθώς και στην αξιολόγηση της ασφάλειας, της κλινικής αποτελεσματικότητας και της σχέσης κόστους οφέλους από την εφαρμογή αυτών των προγνωστικών μοντέλων στην κλινική πράξη μέσω μελετών επιρροής. Ο τρίτος στόχος της διδακτορικής διατριβής ήταν η περαιτέρω διερεύνηση της συσχέτισης της έκθεσης στο κάπνισμα με τον κίνδυνο εμφάνισης ΙΠΙ και η διευκρίνηση αν οι ποικίλες εκθέσεις σε καπνό αλληλεπιδρούν μεταξύ τους. Σχεδιάστηκε μία προοπτική μελέτη κοόρτης στην μελέτη UK Biobank. Η μελέτη αυτή περιλάμβανε 437.000 Καυκάσιους, χωρίς κάποια συγγένεια μεταξύ τους. Εξετάστηκε η επίδραση εκθέσεων σχετικών με το κάπνισμα στον κίνδυνο για ΙΠΙ με πολυμεταβλητά μοντέλα παλινδρόμησης Cox σταθμισμένα για την ηλικία, το φύλο, τον δείκτη κοινωνικοοικονομικού επιπέδου Townsend και την πυκνότητα κατοικίας στην περιοχή διαμονής. Ακόμη εξετάστηκε η παρουσία αθροιστικής και πολλαπλασιαστικής αλληλεπίδρασης μεταξύ των εκθέσεων. Η τεχνική της πολλαπλής αντικατάστασης με αλυσιδωτές εξισώσεις εφαρμόστηκε για τις ελλείπουσες τιμές. Αναγνωρίστηκαν 802 νέα περιστατικά ΙΠΙ. Διαπιστώθηκε συσχέτιση μεταξύ της καπνιστικής συνήθειας (HR, 2.12; 95% CI, 1.81-2.47) και του μητρικού καπνίσματος (HR, 1.38; 95% CI, 1.18-1.62) με τον κίνδυνο ΙΠΙ. Στους καπνιστές, παρατηρήθηκε μία δοσο-εξαρτώμενη σχέση μεταξύ των πακετο-ετών καπνίσματος με την πιθανότητα ΙΠΙ (HR για την κατά μία μονάδα αύξηση πακετο-ετών, 1.013; 95% CI, 1.009-1.016). Επιπλέον, παρατηρήθηκε αθροιστική και πολλαπλασιαστική αλληλεπίδραση μεταξύ του μητρικού καπνίσματος και του ενεργητικού καπνίσματος με σχετικό περίσσειο κίνδυνο λόγω της αλληλεπίδρασης ίσο με 1 (95% CI, 0.45-1.54) και αναλογία του λόγου κινδύνων ίση με 1.50 (95% CI, 1.05-2.14). Συμπερασματικά, το ενεργητικό και το μητρικό κάπνισμα αυξάνουν τον κίνδυνο για ΙΠΙ και δρουν συνεργικά. Επίσης, η ένταση του καπνίσματος εμφανίζει δοσο-εξαρτώμενη σχέση με την ΙΠΙ, ενισχύοντας την υπόθεση μίας πιθανά αιτιώδους συσχέτισης. The aim of this PhD thesis was to decipher the etiologic and prognostic factors related to two chronic respiratory diseases that have remarkable morbidity and mortality, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). The first aim of the thesis was to critically appraise the epidemiological credibility of COPD and, to this end, an umbrella review was conducted. A systematic search was performed, to capture systematic reviews and meta-analyses of observational studies on environmental factors and biomarkers for risk of COPD. A set of standardised methodological criteria was applied, based on the level of statistical significance, sample size, between-study heterogeneity and statistical biases. The search yielded 11 eligible papers, including 18 meta-analyses, and 8 eligible papers, that did not perform qualitative synthesis. Eleven associations achieved statistical significance at P < 0.001, thirteen associations presented an I2 >50%, while six associations had evidence of small-study effects and/or excess significance bias. History of tuberculosis or rheumatoid arthritis, exposure to biomass fuels, tobacco smoking and second hand smoking were supported by high epidemiological credibility for an increased risk of COPD. Moreover, highly suggestive evidence was found for increased levels of serum C-reactive protein, and serum fibrinogen in COPD patients compared with healthy controls. To summarize, findings suggests that, while a proportion of COPD patients are non-smokers, only a narrow range of risk factors not related to smoking have been studied for an association with COPD. Furthermore, there is a need to decipher possible protective factors in COPD pathogenesis given that more than a half of ever-smokers do not develop COPD.The second aim of the thesis was to map and assess prognostic models for outcome prediction in patients with COPD. A systematic review was conducted, through a literature search in PubMed until November 2018, and the search was complemented by hand searching references from eligible articles. Eligible articles included studies developing, validating, or updating a prediction model in COPD patients, foccusing on any potential clinical outcome. The systematic search yielded 228 eligible articles, describing the development of 408 prognostic models, the external validation of 38 models, and the validation of 20 prognostic models derived for diseases other than COPD. The 408 prognostic models were developed in three clinical settings: outpatients (239 prognostic models; 59%), patients admitted to hospital (155 prognostic models; 38%), and patients attending the emergency department (14 prognostic models; 3%). Among the 408 prognostic models, the most prevalent outcomes were mortality (209 prognostic models; 51%), risk for acute exacerbation of COPD (42 prognostic models; 10%), and risk for readmission after the index hospital admission (36 prognostic models; 9%). Overall, the most frequently used predictors were age (166 prognostic models; 41%), forced expiratory volume in one second (85 prognostic models; 21%), sex (74 prognostic models; 18%), body mass index (66 prognostic models; 16%), and smoking (65 prognostic models; 16%). . Model discrimination using the C statistic was available for 311 (76%) models, while calibration was examined in 91 (23%) of the developed models. Of the 408 prognostic models, 100 (25%) were internally validated. For 286 (70%) models a model presentation was not available, and only 56 (14%) models were presented through the full equation. 38 models were externally validated, but in only 12 of thesethe validation was performed by a fully independent team. Seven prognostic models were assessed with an overall low risk of bias according to PROBAST. These models were ADO, B-AE-D, B-AE-D-C, extended ADO, updated ADO, updated BODE, and a model developed by Bertens et al. A meta-analysis of C statistics was performed for 12 prognostic models, and the summary estimates ranged from 0.611 to 0.769.The findings of the systematic review indicated several methodological pitfalls in the development of prognostic models and a low rate of external validation. Future research should focus on the improvement of existing models through update and external validation, as well as the assessment of the safety, clinical effectiveness, and cost effectiveness of the application of these prognostic models in clinical practice through impact studies.The third aim of the PhD thesis was to examine the association of smoking-related exposures with risk of IPF and potential interaction between them. A prospective cohort study was conducted in UK Biobank, including 437,453 non-related men and women of white ethnic background (aged 40 to 69 at baseline). The effect of tobacco smoking-related exposures on risk for IPF was assessed using Cox regression adjusted for age, sex, Townsend deprivation index, and home area population density. Potential additive and multiplicative interaction was examined between these exposures. Multiple imputation with chained equations was used to deal with missing data. 802 incident IPF cases were identified. An association between smoking status (HR, 2.12; 95% CI, 1.81-2.47) and maternal smoking (HR, 1.38; 95% CI, 1.18-1.62) was depicted with risk for IPF in the multivariable model. In ever smokers, a dose-response relationship was observed between pack-years of smoking and risk of IPF (HR per 1 pack-year increase, 1.013; 95% CI, 1.009-1.016). Furthermore, an additive and multiplicative interaction was observed between maternal smoking and smoking status with a relative excess risk due to interaction of 1.00 (95% CI, 0.45-1.54) and a ratio of HR of 1.50 (95% CI, 1.05-2.14). To sum up, active and maternal tobacco smoking have a detrimental effect on risk of IPF and work synergistically. Also, intensity of smoking presents a dose-response association with IPF, strengthening the hypothesis for a potentially causal association. 240 σ.

Background FIBRONET was an observational, multicentre, prospective cohort study investigating the baseline characteristics, clinical course of disease and use of antifibrotic treatment in Italian patients with idiopathic pulmonary fibrosis (IPF). Methods Patients aged ≥ 40 years diagnosed with IPF within the previous 3 months at 20 Italian centres were consecutively enrolled and followed up for 12 months, with evaluations at 3, 6, 9 and 12 months. The primary objective was to describe the clinical course of IPF over 12 months of follow-up, including changes in lung function measured by % predicted forced vital capacity (FVC% predicted). Results 209 patients (82.3% male, mean age 69.54 ± 7.43 years) were enrolled. Mean FVC% predicted was relatively preserved at baseline (80.01%). The mean time between IPF diagnosis and initiation of antifibrotic therapy was 6.38 weeks; 72.3% of patients received antifibrotic therapy within the first 3 months of follow-up, and 83.9% within 12 months of follow-up. Mean FVC% predicted was 80.0% at baseline and 82.2% at 12 months, and 47.4% of patients remained stable (i.e. had no disease progression) in terms of FVC% predicted during the study. Conclusions FIBRONET is the first prospective, real-life, observational study of patients with IPF in Italy. The short time between diagnosis and initiation of antifibrotic therapy, and the stable lung function between baseline and 12 months, suggest that early diagnosis and prompt initiation of antifibrotic therapy may preserve lung function in patients with IPF. Trial registration: NCT02803580

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with an estimated median survival time of 3–5 years after diagnosis. This condition occurs primarily in elderly subjects, and epidemiological studies suggest that the main risk factors, ageing and exposure to cigarette smoke, are associated with both pulmonary and extrapulmonary comorbidities (defined as the occurrence of two or more disorders in a single individual). Ageing and senescence, through interactions with environmental factors, may contribute to the pathogenesis of IPF by various mechanisms, causing lung epithelium damage and increasing the resistance of myofibroblasts to apoptosis, eventually resulting in extracellular matrix accumulation and pulmonary fibrosis. As a paradigm, syndromes featuring short telomeres represent archetypal premature ageing syndromes and are often associated with pulmonary fibrosis. The pathophysiological features induced by ageing and senescence in patients with IPF may translate to pulmonary and extrapulmonary features, including emphysema, pulmonary hypertension, lung cancer, coronary artery disease, gastro-oesophageal reflux, diabetes mellitus and many other chronic diseases, which may lead to substantial negative consequences in terms of various outcome parameters in IPF. Therefore, the careful diagnosis and treatment of comorbidities may represent an outstanding chance to improve quality of life and survival, and it is necessary to contemplate all possible management options for IPF, including early identification and treatment of comorbidities.

Liquid biopsy, which allows the isolation of circulating cell-free (ccf) DNA from blood, is an emerging noninvasive tool widely used in oncology for diagnostic and prognosis purposes. Previous data have shown that serum cfDNA discriminates idiopathic pulmonary fibrosis (IPF) from other interstitial lung diseases. Our study aimed to measure plasma levels of ccfDNA in 59 consecutive therapy-naive and clinically stable IPF patients. The single nucleotide polymorphism (SNP) of the MUC5B gene promoter (rs35705950), associated with increased susceptibility of developing IPF, has been sought in plasma cfDNA and genomic DNA for comparison. Thirty-five age- and sex-matched healthy volunteers were recruited as the control group. Our results show that concentrations of small-size ccfDNA fragments were significantly higher in IPF patients than in controls and inversely correlated with lung function deterioration. Moreover, the median level of 104 ng/mL allowed discriminating patients with mild disease from those more advanced. The rs35705950 polymorphism was found in 11.8% of IPF patients and 8% of controls, with no differences. Complete concordance between ccfDNA and genomic DNA was detected in all control samples, while four out of seven IPF cases (57%) carrying the rs35705950 polymorphism were discordant from genomic DNA (7% of total IPF). Liquid biopsy is a suitable tool with optimistic expectations of application in the field of IPF. In analogy with cancer biology, finding some discrepancies between ccfDNA and genomic DNA in IPF patients suggests that the former may convey specific genetic information present in the primary site of the disease.

Nonidiopathic pulmonary fibrosis (non-IPF) progressive fibrotic interstitial lung diseases (PF-ILDs) are a heterogeneous group of ILDs, often challenging to diagnose, although an accurate diagnosis has significant implications for both treatment and prognosis. A subgroup of these patients experiences progressive deterioration in lung function, physical performance, and quality of life after conventional therapy. Risk factors for ILD progression include older age, lower baseline pulmonary function, and a usual interstitial pneumonia pattern. Management of non-IPF P-ILD is both pharmacologic and nonpharmacologic. Antifibrotic drugs, originally approved for IPF, have been considered in patients with other fibrotic ILD subtypes, with favorable results in clinical trials.

The intracellular tyrosine kinase inhibitor nintedanib has shown great efficacy for the treatment of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases. However, the incidence rate of myocardial infarction (MI) among participants in landmark IPF trials was remarkable, peaking at 3/100 patient-years. Although subjects with IPF often have a high cardiovascular (CV) risk profile, the occurrence of MI in nintedanib-treated patients may not be fully explained by clustering of CV risk factors. Nintedanib inhibits the vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor pathways, which play important roles in the biology of the atherosclerotic plaque and in the response of the heart to ischaemia. Hence, unwanted CV effects may partly account for nintedanib-related MI. We review the evidence supporting this hypothesis and discuss possible actions for a safe implementation of nintedanib in clinical practice, building on the experience with tyrosine kinase inhibitors acquired in cardio-oncology.

Introduction Main clinical manifestations of SARS-CoV-2 infection are characterized by fever, cough, dyspnoea and interstitial pneumonia frequently evolving in an acute respiratory distress syndrome (ARDS). Areas covered Features of coronavirus disease 2019 (COVID-19) pneumonia presents some common points with interstitial lung disease (ILD) both idiopathic and related to rheumatoid arthritis (RA), typically characterized by a chronic progression over some years and possibly complicated by acute exacerbation. The study of some common pathogenetic mechanisms, such as the involvement of the toll-like receptor 4 (TLR4), could contribute to the knowledge and treatment of idiopathic and RA-ILD. Moreover, the hyper-inflammation, mainly characterized by increase of effector T cells and inflammatory cytokines, and the activation of coagulation cascade, observed in COVID-19 related ARDS have been already shown in patients with acute exacerbation of idiopathic and RA-ILD. A literature search was performed some electronic databases, including PubMed, Embase, Scopus, and Web of Science, together with a manual search in COVID-resource centres of the main journals. Expert opinion Despite the uncertainty about many pathogenetic aspects about COVID-19-related pneumonia, we are probably observing a possible model for other forms of ILD and AE. The great amount of data deriving from studies on COVID-19 could be helpful in proposing a safe therapeutic approach for RA-ILD, in understanding pathogenesis of UIP related to autoimmune systemic diseases and to develop new therapeutic strategies for AE.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pneumonia (IP) with poor prognosis. Acute exacerbation (AE) of IPF (AE-IPF) has a substantial and sometimes fatal impact on prognosis. An effective pharmaceutical treatment for AE-IPF is lacking. Macrolides (MACs) have an anti-bacterial activity and anti-inflammatory effects, and IPF treatment with these agents has been recently reported. This report describes a case of infection-triggered AE-IPF treated with corticosteroids (CSs) combined with MACs. A 61-year-old male patient suffering from IPF previously treated with methyl-prednisolone (mPSL) (8 mg/day) was admitted because of fever, dry cough, and dyspnea. Reticular opacities (RO) on chest roentgenogram and ground-glass opacities (GGO) on high-resolution computed tomography (HRCT) exacerbated. The patient was diagnosed with influenza A and influenza A-triggered AE-IPF and was treated with peramivir and mPSL (1 g/day) for 3 days. RO on chest roentgenogram further exacerbated, prompting the addition of erythromycin (EM), in consideration of its anti-inflammatory effects. Thereafter, the patient was successfully treated with mPSL or PSL combined with EM. During the clinical course, he experienced cytomegalovirus (CMV)-induced IP and/or CMV-triggered AE-IPF, being successfully treated with ganciclovir and mPSL or PSL combined with EM. Thereafter, the patient was treated with CSs combined with EM or clarithromycin. Approximately 3 months after initiating EM, RO on chest roentgenogram and GGO on HRCT considerably improved. This case shows that treatment with CSs combined with MACs may be effective in some cases of infection-triggered AE-IPF.

Background Idiopathic pulmonary fibrosis (IPF) is a complex disease with a highly variable clinical course and generally poor prognosis. Classified as a rare disease, significant increases in incidence have been recorded worldwide in recent years. Left untreated IPF is extremely debilitating with substantial personal, social and economic implications. Objectives To discuss how IPF is diagnosed and managed in real life clinical practice with particular reference to Italy and to determine how new and effective therapies can be incorporated into a patient-centred management approach in order to improve the lives of patients with IPF. Outcomes Barriers to early diagnosis are discussed. Cited reasons for delays in diagnosing IPF in Italy include: inherent difficulties in diagnosis; lack of knowledge/awareness of the condition among point-of-contact healthcare professionals; delays in referral to centres of excellence and underestimation of symptoms by both patients and healthcare workers. Valid therapeutic options with demonstrated efficacy in slowing the decline in lung function are now available for patients with IPF. The ASCEND trial confirmed the effects of pirfenidone, approved for the treatment of IPF on the basis of the four phase III trials. Nintedanib, a tyrosine kinase inhibitor that targets the PDGF receptors α/β, FGF receptors 1 to 3, and VEGF receptors 1–3, is approved in the USA and the EU for the treatment of IPF. The TOMORROW and the INPULSIS placebo controlled trials in patients with IPF confirm the efficacy and safety of nintedanib and recent interim analyses endorse its long-term effects in slowing disease progression. Conclusions The importance of early and accurate diagnosis of IPF cannot be underestimated and it is the duty of all healthcare professionals to be vigilant to the symptoms of IPF and to involve a multidisciplinary team in diagnosing and managing IPF early in the course of disease.

In idiopathic pulmonary fibrosis (IPF), several factors may have a negative impact on the nutritional status, including an increased respiratory muscles load, release of inflammation mediators, the coexistence of hypoxemia, and physical inactivity. Nutritional abnormalities also have an impact on IPF clinical outcomes. Given the relevance of nutritional status in IPF patients, we sought to focus on some critical issues, highlighting what is known and what should be further learned about these issues. We revised scientific literature published between 1995 and August 2019 by searching on Medline/PubMed and EMBASE databases including observational and interventional studies. We conducted a narrative review on nutritional assessment in IPF, underlining the importance of nutritional evaluation not only in the diagnostic process, but also during follow-up. We also highlighted the need to keep a high level of attention on cardiovascular comorbidities. We also focused on current clinical treatment in IPF with Nintedanib and Pirfenidone and management of gastrointestinal adverse events, such as diarrhea, induced by these antifibrotic drugs. Finally, we concentrated on the importance of pulmonary rehabilitation program, including nutritional assessment, education and behavioral change, and psychological support among its essential components. More attention should be devoted to the assessment of the undernutrition and overnutrition, as well as of muscle strength and physical performance in IPF patients, taking also into account that an adequate clinical management of gastrointestinal complications makes IPF drug treatments more feasible.

Dendritic cells (DCs) accumulate in the lung of patients affected by idiopathic pulmonary fibrosis (IPF). We measured the frequencies of circulating conventional CD1c + and CD141+ cells (namely, cDC2 and cDC1) and of plasmacytoid CD303+ DCs in a cohort of 60 therapy naive IPF patients by flow cytometry. Peripheral levels of reactive oxygen species (ROS) and of pro-inflammatory and Th1/Th2 polarizing cytokines were also analyzed. All blood DC subtypes were significantly reduced in IPF patients in comparison to age- and sex-matched controls, while ROS and interleukin (IL-6) levels were augmented. IL-6 expression increased along with disease severity, according to the gender-age-physiology index, and correlated with the frequency of cDC2. IL-6 and cDC2 were not influenced by anti-fibrotic therapies but were associated with a reduced survival, the latter being an independent predictive biomarker of worse prognosis. Deciphering the role of DCs in IPF might provide information on disease pathogenesis and clinical behavior.

Despite the fact that epithelial-mesenchymal transition (EMT) is a common downstream mechanism of all fibrosing diseases, whether it represents a leading process in the development of idiopathic pulmonary fibrosis has been widely discussed and is still a matter of debate. According to the most recent advances, EMT is thought to be mainly driven by the overexpression of several developmental pathways upstream of dysfunctional epithelial regeneration, which indeed normally occurs after damage and during tissue turnover. Future research should likely be directed at investigating the molecular mechanisms underlying epithelial dysfunction, in order to allow for both the removal of the wording "idiopathic" from idiopathic pulmonary fibrosis ("IPF") and for the identification of earlier and more effective therapeutic targets than the late process of fibrosis.

Clinical case We describe the case of a 50-y-old man with idiopathic pulmonary fibrosis (IPF) who underwent pulmonary rehabilitation (PR). The 8-wk training program, including resistance training and aerobic exercises, was conducted 3 d/wk under physiotherapist supervision. Clinical and functional assessment was performed prior to and following the program. At the end of the training program, meaningful improvements in primary outcomes, including spirometry values and exertional parameters, were noted. Discussion Pulmonary rehabilitation may represent a valid treatment in the management of symptoms in patients with IPF. Although the current guidelines for diagnosis and management of IPF recommend the use of PR programs, patients are not routinely referred to PR centers and exercise training for these patients is not standardized. Summary Idiopathic pulmonary fibrosis is a progressive and fatal disease characterized by the loss of lung function, which results in a severe impairment of daily activities. Prospective studies testing the effectiveness of PR programs in larger cohorts of patients are still lacking. Furthermore, a standardization of pulmonary training programs should be developed to better understand the benefit of PR.

There is evidence that hypopneas are more common than apneas in obstructive sleep apnea (OSA) related to idiopathic pulmonary fibrosis (IPF). We investigated the frequency distribution of hypopneas in 100 patients with interstitial lung diseases (ILDs) (mean age 69 yrs &plusmn, 7.8, 70% males), including 54 IPF cases, screened for OSA by home sleep testing. Fifty age- and sex-matched pure OSA patients were included as controls. In ILD-OSA patients the sleep breathing pattern was characterized by a high prevalence of hypopneas that were preceded by hyperpnea events configuring a sort of periodic pattern. This finding, we arbitrarily defined hyperpnea&ndash, hypopnea periodic breathing (HHPB), was likely reflecting a central event and was completely absent in control OSA. Also, the HHPB was highly responsive to oxygen but not to the continuous positive pressure support. Thirty-three ILD-OSA patients (42%) with a HHPB associated with a hypopnea/apnea ratio &ge, 3 had the best response to oxygen with a median residual AHI of 2.6 (1.8&ndash, 5.6) vs. 28.3 (20.7&ndash, 37.8) at baseline (p &lt, 0.0001). ILD-OSA patients with these characteristics were similarly distributed in IPF (54.5%) and no-IPF cases (45.5%), the most of them being affected by moderate&ndash, severe OSA (p = 0.027). Future studies addressing the pathogenesis and therapy management of the HHPB should be encouraged in ILD-OSA patients.

Background Idiopathic Pulmonary Fibrosis (IPF) is an aggressive interstitial lung disease with an unpredictable course. Occupational dust exposure may contribute to IPF onset, but its impact on antifibrotic treatment and disease prognosis is still unknown. We evaluated clinical characteristics, respiratory function and prognostic predictors at diagnosis and at 12 month treatment of pirfenidone or nintedanib in IPF patients according to occupational dust exposure. Methods A total of 115 IPF patients were recruited. At diagnosis, we collected demographic, clinical characteristics, occupational history. Pulmonary function tests were performed and two prognostic indices [Gender, Age, Physiology (GAP) and Composite Physiologic Index (CPI)] calculated, both at diagnosis and after the 12 month treatment. The date of long-term oxygen therapy (LTOT) initiation was recorded during the entire follow-up (mean = 37.85, range 12–60 months). Results At baseline, patients exposed to occupational dust [≥ 10 years (n = 62)] showed a lower percentage of graduates (19.3% vs 54.7%; p = 0.04) and a higher percentage of asbestos exposure (46.8% vs 18.9%; p 0.002) than patients not exposed [

Alveolar type II (ATII) cells are a key structure of the distal lung epithelium, where they exert their innate immune response and serve as progenitors of alveolar type I (ATI) cells, contributing to alveolar epithelial repair and regeneration. In the healthy lung, ATII cells coordinate the host defense mechanisms, not only generating a restrictive alveolar epithelial barrier, but also orchestrating host defense mechanisms and secreting surfactant proteins, which are important in lung protection against pathogen exposure. Moreover, surfactant proteins help to maintain homeostasis in the distal lung and reduce surface tension at the pulmonary air–liquid interface, thereby preventing atelectasis and reducing the work of breathing. ATII cells may also contribute to the fibroproliferative reaction by secreting growth factors and proinflammatory molecules after damage. Indeed, various acute and chronic diseases are associated with intensive inflammation. These include oedema, acute respiratory distress syndrome, fibrosis and numerous interstitial lung diseases, and are characterized by hyperplastic ATII cells which are considered an essential part of the epithelialization process and, consequently, wound healing. The aim of this review is that of revising the physiologic and pathologic role ATII cells play in pulmonary diseases, as, despite what has been learnt in the last few decades of research, the origin, phenotypic regulation and crosstalk of these cells still remain, in part, a mystery.