Clinical review: Idiopathic pulmonary fibrosis acute exacerbations - unravelling Ariadne's thread

Idiopathic pulmonary fibrosis (IPF) is a dreadful, chronic, and irreversibly progressive fibrosing disease leading to death in all patients affected, and IPF acute exacerbations constitute the most devastating complication during its clinical course. IPF exacerbations are subacute/acute, clinically significant deteriorations of unidentifiable cause that usually transform the slow and more or less steady disease decline to the unexpected appearance of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) ending in death. The histological picture is that of diffuse alveolar damage (DAD), which is the tissue counterpart of ARDS, upon usual interstitial pneumonia, which is the tissue equivalent of IPF. ALI/ARDS and acute interstitial pneumonia share with IPF exacerbations the tissue damage pattern of DAD. 'Treatment' with high-dose corticosteroids with or without an immunosuppressant proved ineffective and represents the coup de grace for these patients. Provision of excellent supportive care and the search for and treatment of the 'underlying cause' remain the only options. IPF exacerbations require rapid decisions about when and whether to initiate mechanical support. Admission to an intensive care unit (ICU) is a particular clinical and ethical challenge because of the extremely poor outcome. Transplantation in the ICU setting often presents insurmountable difficulties

MRC chronic Dyspnea Scale: Relationships with cardiopulmonary exercise testing and 6-minute walk test in idiopathic pulmonary fibrosis patients: a prospective study

<p>Abstract</p> <p>Background</p> <p>Exertional dyspnea is the most prominent and disabling feature in idiopathic pulmonary fibrosis (IPF). The Medical Research Chronic (MRC) chronic dyspnea score as well as physiological measurements obtained during cardiopulmonary exercise testing (CPET) and the 6-minute walk test (6MWT) are shown to provide information on the severity and survival of disease.</p> <p>Methods</p> <p>We prospectively recruited IPF patients and examined the relationship between the MRC score and either CPET or 6MWT parameters known to reflect physiologic derangements limiting exercise capacity in IPF patients</p> <p>Results</p> <p>Twenty-five patients with IPF were included in the study. Significant correlations were found between the MRC score and the distance (r = -.781, p < 0.001), the SPO₂at the initiation and the end (r = -.542, p = 0.005 and r = -.713, p < 0.001 respectively) and the desaturation index (r = .634, p = 0.001) for the 6MWT; the MRC score and <it>V</it>O₂peak/kg (r = -.731, p < 0.001), SPO₂at peak exercise (r = -. 682, p < 0.001), VE/VCO₂slope (r = .731, p < 0.001), VE/VCO₂at AT (r = .630, p = 0.002) and the Borg scale at peak exercise (r = .50, p = 0.01) for the CPET. In multiple logistic regression analysis, the only variable independently related to the MRC is the distance walked at the 6MWT.</p> <p>Conclusion</p> <p>In this population of IPF patients a good correlation was found between the MRC chronic dyspnoea score and physiological parameters obtained during maximal and submaximal exercise testing known to reflect ventilatory impairment and exercise limitation as well as disease severity and survival. This finding is described for the first time in the literature in this group of patients as far as we know and could explain why a simple chronic dyspnea score provides reliable prognostic information on IPF.</p

Beliefs and preferences regarding biological treatments for severe asthma

Background: Severe asthma is a serious condition with a significant burden on patients' morbidity, mortality, and quality of life. Some biological therapies targeting the IgE and interleukin-5 (IL5) mediated pathways are now available. Due to the lack of direct comparison studies, the choice of which medication to use varies. We aimed to explore the beliefs and practices in the use of biological therapies in severe asthma, hypothesizing that differences will occur depending on the prescribers’ specialty and experience. Methods: We conducted an online survey composed of 35 questions in English. The survey was circulated via the INterasma Scientific Network (INESNET) platform as well as through social media. Responses from allergists and pulmonologists, both those with experience of prescribing omalizumab with (OMA/IL5) and without (OMA) experience with anti-IL5 drugs, were compared. Results: Two hundred eighty-five (285) valid questionnaires from 37 countries were analyzed. Seventy-on percent (71%) of respondents prescribed biologics instead of oral glucocorticoids and believed that their side effects are inferior to those of Prednisone 5 mg daily. Agreement with ATS/ERS guidelines for identifying severe asthma patients was less than 50%. Specifically, significant differences were found comparing responses between allergists and pulmonologists (Chi-square test, p &lt; 0.05) and between OMA/IL5 and OMA groups (p &lt; 0.05). Conclusions: Uncertainties and inconsistencies regarding the use of biological medications have been shown. The accuracy of prescribers to correctly identify asthma severity, according to guidelines criteria, is quite poor. Although a substantial majority of prescribers believe that biological drugs are safer than low dose long-term treatment with oral steroids, and that they must be used instead of oral steroids, every effort should be made to further increase awareness. Efficacy as disease modifiers, biomarkers for selecting responsive patients, timing for outcomes evaluation, and checks need to be addressed by further research. Practices and beliefs regarding the use of asthma biologics differ between the prescriber's specialty and experience; however, the latter seems more significant in determining beliefs and behavior. Tailored educational measures are needed to ensure research results are better integrated in daily practice

Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: An international case-cohort study

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts. A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (\u3baw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the Cindex. A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (\u3baw=0.65, IQR 0.53-0.72, p20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75). Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts

Sleep breathing disorders in patients with idiopathic pulmonary fibrosis (IPF)

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic irreversible diffuse interstitial lung disease of unknown etiology, characterized by progressive destruction of normal lung architecture and scarring of the lung parenchyma with the histologic / radiologic pattern of usual interstitial pneumonia (UIP). It is a fatal disease, with a median survival of three years after diagnosis, without effective treatment apart from medications that delay disease progression, treatment of respiratory failure and comorbidities when they occur. According to recent scientific data, sleep breathing disorders represent one of the most common comorbidities in IPF but have not been adequately studied.Aim: The description and study of sleep breathing disorders (SBDs) in patients with idiopathic pulmonary fibrosis (IPF), their relationship to clinical, functional and physiological parameters of disease and the study of their effect on survival and quality of sleep and life of patients with IPF.Μethods: In a group of 31 treatment naïve newly diagnosed patients with IPF who fulfilled the international diagnostic criteria of IPF / UIP, we prospectively studied sleep parameters with polysomnography. We prospectively investigated the relationship of SBD parameters such as apnea hypopnea index (AHI), maximal difference in oxygen saturation between wakefulness and sleep (maxdiff SpO2), and lowest sleep oxygen saturation (lowest SpO2) with clinical (survival, dyspnea, daytime sleepiness), pulmonary function, submaximal [6-min walk test (6MWT)] and maximal exercise variables [cardiopulmonary exercise test (CPET)], and right ventricular systolic pressure (RVSP) as well as with parameters of quality of life and sleep.Results: We found that obstructive sleep apnea syndrome (OSAS), defined by AHI>5, occurs at a rate of 90.3% in patients with IPF. Among the characteristics of sleep, oxygen desaturation during sleep significantly exceeded that of maximum exercise, and both parameters examined (the maxdiff-SaO2 and minimum SaO2 during sleep) were associated with survival. Maxdiff-SaO2 correlated inversely with DLCO% and SaO2 after 6MWT, and directly to the MRC, the AHI and RVSP, whereas the minimum SaO2 during sleep was related directly with functional parameters (TLC%, DLCO% ) as well as physiological parameters of exercise tests (6MWT distance, SaO2 after 6MWT, VO2 peak / kg, SaO2 peak), and inversely with the MRC, AHI and RVSP.After exclusion of the subgroup of patients with IPF who had been treated with CPAP for OSAS, AHI was associated with significantly decreased survival.Also, a significant correlation emerged between both desaturation parameters examined [ minimum SaO2 during sleep, the difference in oxygen saturation between wakefulness and sleep (maxdiff-SaO2)] and the RVSP with the questionnaire related to sleep-related quality of life (FOSQ, Functional Outcome of Sleep Questionnaire), the Athens insomnia scale (AIS, Athens Insomnia Scale) and Beck depression questionnaire (BDI, Beck Depression Inventory).Conclusions The main finding of this study is that in patients with IPF, intermittent sleep oxygen desaturation exceeds significantly that of maximal exercise and is associated with survival. Both sleep oxygen desaturation variables studied (maxdiff-SaO2, minimum SaO2), significantly correlated not only with survival but also with lung injury, as reflected by functional parameters (TLC%, DLCO%), sleep apneas-hypopneas, exercise oxygen desaturation, breathlessness, and systolic right ventricular pressure (RVSP). These results suggest that in patients with IPF a potential relationship and interaction exists between the degree of lung injury and sleep-apnea events in the generation, induction, and the size of the intermittent oxygen desaturation during sleep, and hence the role that desaturation may have in the burden of pulmonary hypertension and to the negative impact on survival of patients with IPF. Further studies are needed to clarify this issue and underlying pathophysiological mechanisms.Εισαγωγή: Η ιδιοπαθής πνευμονική ίνωση (IPF) είναι μία χρόνια μη αναστρέψιμη διάχυτη διάμεση πνευμονοπάθεια άγνωστης αιτιολογίας, η οποία χαρακτηρίζεται από την προοδευτική καταστροφή της φυσιολογικής αρχιτεκτονικής των πνευμόνων και την ουλοποίηση του πνευμονικού παρεγχύματος με το ιστολογικό/ακτινολογικό πρότυπο της συνήθους διάμεσης πνευμονίας (UIP). Είναι θανατηφόρος νόσος, με διάμεση επιβίωση τρία έτη από την διάγνωση, χωρίς αποτελεσματική θεραπεία πέραν από την προσπάθεια φαρμακευτικής επιβράδυνσης της πορείας της νόσου, την αντιμετώπιση της αναπνευστικής ανεπάρκειας όταν αυτή προκύπτει καθώς και των συννοσηροτήτων. Σύμφωνα με σχετικά πρόσφατα επιστημονικά δεδομένα, οι διαταραχές της αναπνοής στον ύπνο αποτελούν μια από τις συχνότερες συννοσηρότητες στην IPF που όμως δεν έχουν μελετηθεί επαρκώς.Σκοπός: Η περιγραφή και μελέτη των διαταραχών της αναπνοής στον ύπνο (SBDs) σε ασθενείς με ιδιοπαθή πνευμονική ίνωση (IPF) και ο τρόπος που αυτές σχετίζονται με κλινικούς, λειτουργικούς και φυσιολογικούς δείκτες της νόσου καθώς και η μελέτη της επίδρασης τους στην επιβίωση και στην ποιότητα ύπνου και ζωής των ασθενών με IPF.Μέθοδος: Σε μία ομάδα 31 πρωτοδιαγνωσμένων ασθενών με IPF οι οποίοι δεν ελάμβαναν θεραπευτική αγωγή και πληρούσαν τα διεθνή διαγνωστικά κριτήρια της IPF/UIP, μελετήσαμε προοπτικά παραμέτρους του ύπνου με πολυκαταγραφική μελέτη ύπνου και στη συνέχεια εξετάσαμε τη σχέση των SBDs παραμέτρων με την επιβίωση καθώς και με κλινικούς δείκτες, δείκτες πνευμονικής λειτουργίας όπως αυτοί αντικατοπτρίζονται στον πλήρη λειτουργικό έλεγχο της αναπνοής και στις δοκιμασίες άσκησης, με την πνευμονική υπέρταση όπως αυτή αντικατοπτρίζεται στη συστολική πίεση της δεξιάς κοιλίας (RVSP) από το υπερηχογράφημα καρδιάς καθώς και με παραμέτρους της ποιότητας ζωής.Αποτελέσματα: Διαπιστώσαμε ότι το σύνδρομο αποφρακτικής άπνοιας στον ύπνο (OSAS), έτσι όπως ο δείκτης AHI>5 καθορίζει, απαντάται σε ποσοστό 90.3% των ασθενών με IPF που μελετήθηκαν. Μεταξύ των χαρακτηριστικών του ύπνου, οι αποκορεσμοί οξυγόνου κατά την διάρκεια του ύπνου υπερέβησαν στατιστικά σημαντικά εκείνους της μέγιστης άσκησης ενώ και οι δύο παράμετροι που εξετάστηκαν (η διαφορά του κορεσμού σε οξυγόνο μεταξύ εγρήγορσης και ύπνου- maxdiff-SaO2 και ο ελάχιστος SaO2 κατά τη διάρκεια του ύπνου) σχετίζονταν με την επιβίωση. Ακόμα η maxdiff-SaO2 συσχετιζόταν αντιστρόφως ανάλογα με την DLCO% και τον SaO2 μετά 6MWT, και ανάλογα με την MRC, τον ΑΗΙ και την RVSP, ενώ ο ελάχιστος SaO2 κατά τη διάρκεια του ύπνου σχετιζόταν ανάλογα με λειτουργικές παραμέτρους (TLC%, DLCO%) καθώς και με φυσιολογικές παραμέτρους δοκιμασιών άσκησης (6MWT απόσταση, SaO2 μετά 6MWT, VO2 peak/kg, SaO2 peak) και αντιστρόφως ανάλογα με τις MRC, AHI και RVSP.Μετά από αποκλεισμό της υποομάδας των ασθενών με IPF που είχαν τεθεί σε θεραπεία με CPAP για OSAS, και ο ΑΗΙ βρέθηκε να συσχετίζεται σημαντικά με μειωμένη επιβίωση.Επίσης, αναδείχθηκε σημαντική συσχέτιση μεταξύ των δύο παραμέτρων αποκορεσμού που εξετάστηκαν [του ελάχιστου SaO2 κατά τη διάρκεια του ύπνου, της διαφοράς του κορεσμού σε οξυγόνο μεταξύ εγρήγορσης και ύπνου (maxdiff-SaO2)] καθώς και της RVSP με το ερωτηματολόγιο για την ποιότητα ζωής σχετιζόμενης με τον ύπνο (FOSQ Functional Outcome of Sleep Questionnaire), την κλίμακα αϋπνίας Αθηνών (AIS Athens Insomnia Scale) και το ερωτηματολόγιο κατάθλιψης του Beck (BDI Beck Depression Inventory).Συμπεράσματα: Το κύριο εύρημα της παρούσας μελέτης είναι ότι στους ασθενείς με ΙPF, οι αποκορεσμοί οξυγόνου κατά την διάρκεια του ύπνου υπερβαίνουν εκείνον της μέγιστης άσκησης, και σχετίζονται με την επιβίωση. Και οι δύο παράμετροι αποκορεσμού οξυγόνου στον ύπνο (maxdiff-SaO2, ελάχιστος SaO2) τις οποίες εξετάσαμε συσχετίζονταν σημαντικά όχι μόνο με την επιβίωση αλλά και με την πνευμονική βλάβη, όπως αυτή αντικατοπτρίζεται από τις λειτουργικές παραμέτρους (TLC %, DLCO %), τα υπνο-απνοϊκά επεισόδια, τον αποκορεσμό οξυγόνου στην άσκηση, την δύσπνοια, και την συστολική πίεση της δεξιάς κοιλίας (RVSP). Τα αποτελέσματα αυτά υποδηλώνουν πιθανά ότι σε ασθενείς με IPF υπάρχει σχέση και αλληλεπίδραση μεταξύ του βαθμού της πνευμονικής βλάβης και των υπνο-απνοικών επεισοδίων στην γένεση, επαγωγή και το μέγεθος των διαλειπόντων αποκορεσμών οξυγόνου κατά την διάρκεια του ύπνου και κατά συνέπεια στον ρόλο που ο αποκορεσμός μπορεί να έχει στην επιβάρυνση της πνευμονικής υπέρτασης και στην αρνητική επίδραση στην επιβίωση των ασθενών με IPF

Existing and emerging treatments for idiopathic pulmonary fibrosis

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive and invariable fatal interstitial lung disease. Current antifibrotic treatment halts disease progression but does not cure the disease itself. In the last decade, a substantial understanding of disease pathobiological mechanisms led to the development of numerous clinical trials testing promising pharmacologic agents. Areas covered: In this review, we summarize and discuss current and emerging pharmacological therapies for IPF and highlight the potential of different promising investigational compounds in phase II-IV trials with positive or pending results. Expert commentary: Existing therapies for IPF slow disease progression and recent advances in understanding IPF complex pathogenesis unfolded multiple new possible therapeutic targets. A relevant number of promising clinical trials targeted specific biologic pathways, are ongoing or upcoming, but we are far away from a definitive cure of IPF soon. An ‘oncologic approach’ via tailoring medicine could be a realistic therapeutic intervention that may improve expectancy and quality of life in IPF. © 2019, © 2019 Informa UK Limited, trading as Taylor &amp; Francis Group

Idiopathic pulmonary fibrosis acute exacerbations: Where are we now?

Considerable controversy is haunting the treatment of IPF &apos;acute exacerbation&apos;, its most devastating complication. The consensus coined term &apos;acute exacerbation&apos; implies that on an unknown etiology disease such as IPF, an unknown etiology superimposed acute lung injury/acute respiratory distress syndrome (ALI/ARDS) represents the end-life event in a consistent proportion of patients and are treated by high dose steroids despite unproven benefit. Inversely, ALI/ARDS treatment recommendations are based on the provision of excellent supportive care plus an extensive search and appropriate treatment of the etiologic precipitant and all intensive care clinicians in the absence of an obvious etiology, considering that occult infection is the most probable and also the most treatable underlying condition, universally administer extensive spectrum antimicrobials. Viewing the persistent high mortality in IPF &apos;acute exacerbations&apos; treated with steroids we strongly believe that a study comparing the two arms of the steroid and non-steroid approach is greatly awaited by scientists and owed to the patients. © Informa Uk, Ltd