Φαινότυποι της χρόνιας αποφρακτικής πνευμονοπάθειας

Chronic Obstructive Pulmonary Disease (COPD) is defined as persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities usually caused by noxious particles or gases and influenced by host factors. COPD diagnosis requires not only a consistent history but also the presence of airflow limitation in the spirometry. Historically, two phenotypes have been described to further characterize the disease: chronic bronchitis which is associated with airway inflammation and its main characteristic is chronic productive cough, and emphysema which is associated with alveolar destruction and presents with dyspnea. Although, these phenotypes may provide some additional characterization of the pathophysiology of the disease, they are not extensive enough for COPD, which is heterogenous disease, and do not provide phenotypic categorization that indicate specific treatment. Moreover, the current definition of COPD and phenotypes do not include patients with significant respiratory symptoms, a proportion of which have high mortality, who do not have airflow limitation. We describe clinically relevant COPD phenotypes that provide prognostication and/or indicate specific treatment and COPD-like phenotypes that do not necessary meet the current diagnostic criteria for COPD but provide additional prognostication and potentially can indicate response to certain treatments.Η Χρόνια Αποφρακτική Πνευμονοπάθεια (ΧΑΠ) ορίζεται ως επίμονα αναπνευστικά συμπτώματα και περιορισμός της ροής του αέρα στους αεραγωγούς λόγω ανωμαλιών των αεραγωγών και/ή των κυψελιδών του πνεύμονα που προκαλούνται συνήθως από επιβλαβή σωματίδια ή αέρια και επηρεάζονται από παράγοντες ξενιστή. Ιστορικά, δύο φαινότυποι έχουν περιγραφεί για τον περαιτέρω χαρακτηρισμό της νόσου: η χρόνια βρογχίτιδα που σχετίζεται με φλεγμονή των αεραγωγών και το κύριο χαρακτηριστικό της είναι ο χρόνιος παραγωγικός βήχας και το εμφύσημα που σχετίζεται με καταστροφή των των κυψελιδών του πνεύμονα και παρουσιάζεται με δύσπνοια. Αν και, αυτοί οι φαινότυποι μπορεί να παρέχουν κάποιο πρόσθετο χαρακτηρισμό της παθοφυσιολογίας της νόσου, δεν είναι αρκετά εκτενείς για τη ΧΑΠ που είναι μια ετερογενής νόσο και δεν παρέχουν φαινοτυπική κατηγοριοποίηση που υποδεικνύει ειδική θεραπεία. Επιπλέον, ο τρέχων ορισμός της ΧΑΠ δεν περιλαμβάνει ασθενείς με σημαντικά αναπνευστικά συμπτώματα, ένα ποσοστό των οποίων έχει υψηλή θνησιμότητα, οι οποίοι δεν έχουν αποφρακτική φυσιολογία. Σε αυτή τη μελετη περιγράφουμε φαινότυπους της ΧΑΠ που είναι κλινικά χρήσιμοι και παρέχουν πρόσθετη πρόγνωστικη αξία και ενδεχομένως μπορεί να υποδηλώνουν ανταπόκριση σε ορισμένες θεραπείες ή αναφέρονται σε ασθενείς που δυνητικά έχουν ασθένεια με πιθανές θεραπευτικές επιλογές.8Σε αυτή τη διατριβή, δείξαμε ότι ορισμένα χαρακτηριστικά της ανταπόκρισης στα βρογχοδιασταλτικά (συνδυασμένη ανταπόκριση σε FEV1 και FVC) μπορούν να βοηθήσουν στον εντοπισμό ασθενών με ΧΑΠ των οποίων η νόσος μιμειται το άσθμα (Asthma-COPD overlap). Οι ασθενείς με ΧΑΠ που έχουν ανταπόκριση στα βρογχοδιασταλτικά σε κάθε σπιρομέτρηση σε πολλαπλές μετρήσεις φαίνεται να έχουν περισσότερα «ασθματικά» χαρακτηριστικά, μεγαλύτερη επιδείνωση της πνευμονικής λειτουργίας με το πέρασμα του χρόνου, και σοβάροτερη νόσο των μικρών αεραγωγών σε σχέση με εκείνους τους ασθενείς που δεν έχουν ανταπόκριση στα βρογχοδιασταλτικά σε κάθε σπιρομέτρηση. Αυτοί οι ασθενείς μπορεί να έχουν δραματική ανταπόκριση στη βιολογική θεραπεία π.χ. anti-IL5 παρόμοια με την ανταπόκριση που έχουν οι ασθενείς με άσθμα.Επιπλέον, δείξαμε ότι τα άτομα με φυσιολογική σπιρομέτρηση που έχουν συχνές αναπνευστικές παροξύνσεις έχουν αυξημένη θνησιμότητα και διατρέχουν υψηλό κίνδυνο για επιδείνωση της πνευμονικής λειτουργίας και εξέλιξης σε ΧΑΠ. Απαιτείται περαιτέρω έρευνα για να αξιολογηθεί εάν η θεραπεία αυτών των ατόμων που έχουν φυσιολογική σπιρομέτρηση μπορεί να βελτιώσει μακροπρόθεσμα την υγεία τους, συμπεριλαμβανομένης της πρόληψης της εξέλιξης σε ΧΑΠ. Σε άτομα με παθολογική σπιρομέτρηση που δεν είναι αποφρακτική (Preserved Ratio Impaired Spirometry or PRISm), η παγίδευση αέρα είναι παρούσα σε άτομα με συχνές αναπνευστικές9παροξύνσεις, αυξημένη θνησιμότητα, και συνδέεται μα υψηλότερο κίνδυνο εξέλιξης σε ΧΑΠ. Απαιτείται περαιτέρω έρευνα για να αξιολογηθεί εάν τα άτομα με PRISm επωφελούνται από την φαρμακευτικές αγώγες που χρησιμοποιούνται στη ΧΑΠ.Αυτή η περαιτέρω κατηγοριοποιήση της ΧΑΠ σε επιμέρους φαινότυπους που είναι κλινικά χρήσιμοι μπορεί να βοηθήσει στον εντοπισμό ασθενών που ανταποκρίνονται καλά σε υπάρχουσες θεραπείες. Απαιτείται περαιτέρω έρευνα σε εκείνα τα άτομα με αναπνευστικό σύμπτωμα ή με υψηλό κίνδυνο για εξέλιξη σε ΧΑΠ, π.χ. άτομα με βεβαρυμένο ιστορικό καπνίσματος, που δεν έχουν ακόμη αποφρακτική σπιρομέτρηση (κανονική σπιρομέτρηση ή PRISm) για να αξιολογηθεί σε κλινικές δοκιμές αν η θεραπεία αυτών των ατόμων μπορεί να βελτιώσει την υγεία τους, συμπεριλαμβανομένης της πρόληψης της εξέλιξης σε ΧΑΠ

Metabolomics in COPD Acute Respiratory Failure Requiring Noninvasive Positive Pressure Ventilation

We aimed to investigate whether metabolomic analysis can discriminate acute respiratory failure due to COPD exacerbation from respiratory failure due to heart failure and pneumonia. Since COPD exacerbation is often overdiagnosed, we focused on those COPD exacerbations that were severe enough to require noninvasive mechanical ventilation. We enrolled stable COPD subjects and patients with acute respiratory failure requiring noninvasive mechanical ventilation due to COPD, heart failure, and pneumonia. We excluded subjects with history of both COPD and heart failure and patients with obstructive sleep apnea and obstructive lung disease other than COPD. We performed metabolomics analysis using NMR. We constructed partial least squares discriminant analysis (PLS-DA) models to distinguish metabolic profiles. Serum (p=0.001, R2 = 0.397, Q2 = 0.058) and urine metabolic profiles (p<0.001, R2 = 0.419, Q2 = 0.142) were significantly different between the four diagnosis groups by PLS-DA. After excluding stable COPD patients, the metabolomes of the various respiratory failure groups did not cluster separately in serum (p=0.2, R2 = 0.631, Q2 = 0.246) or urine (p=0.065, R2 = 0.602, Q2 = −0.134). However, several metabolites in the serum were reduced in patients with COPD exacerbation and pneumonia. We did not find a metabolic profile unique to COPD exacerbation, but we were able to clearly and reliably distinguish stable COPD patients from patients with respiratory failure in both serum and urine

Home noninvasive ventilation use in patients hospitalized with COPD

Abstract Introduction The study objective was to estimate the prevalence of chronic hypercapnic respiratory failure (CHRF) and home noninvasive ventilation (NIV) use in a high‐risk population, individuals with a history of at least one COPD‐related hospitalizations. Methods We retrospectively analyzed electronic medical record data of patients with at least one COPD‐related hospitalization between October 1, 2011, and September 30, 2017, to the Iowa City VA Medical Center. We excluded individuals with no obstructive ventilatory defect. Results Of 186 patients, the overall prevalence of compensated hypercapnic respiratory failure (CompHRF), defined as PaCO2 > 45 mmHg with a pH = 7.35–7.45, was 52.7%, while the overall prevalence of home NIV was 4.3%. The prevalence of CompHRF was 43.6% and home NIV was 1.8% in those with one COPD‐related hospitalization. Among those with ≥4 COPD‐related hospitalizations, the prevalence of CompHRF was 77.8% (14 of 18), and home NIV was 11.1% (2 of 18). Conclusion Approximately half of individuals with at least one COPD‐related hospitalization have CompHRF, but only 8.2% of those use home NIV. Future studies should estimate CHRF rates and the degree of underutilization of home NIV in larger multicenter samples

Ventilator Settings Can Substantially Impact Patients’ Comfort

With increasing realization that sedatives may complicate care of mechanically ventilated patients, greater emphasis might turn to promoting comfort by titration of ventilator settings. Patients with acute on chronic respiratory failure (ACRF) with underlying chronic obstructive pulmonary disease (COPD) demonstrate different levels of comfort in response to varying ventilator settings compared to those with underlying obesity hypoventilation syndrome (OHS). Patients recovering from ACRF with underlying COPD or OHS were randomized to varying combinations of ventilator modes (assist control and pressure support), tidal volumes, and inspiratory flows for 3 minutes/setting. For each ventilator setting, physiologic variables were recorded and patients indicated their level of comfort using a 10-point Borg scale. In all, 20 patients, aged 68 ± 13 years (standard deviation) and ventilated for 4.9 days, were enrolled. Of 20 patients, 13 had COPD and 7 had OHS. No ventilator mode, flow, or tidal volume provided consistently greater comfort between the groups, but patients reported substantial ranges of comfort (up to 8 Borg points) across the ventilator settings studied. There were no significant differences in heart rate, blood pressure, or airway pressures within patients across ventilator settings or between the groups, but patients with OHS were more tachypneic compared to patients with COPD while breathing on assist control of 6 mL/kg (constant flow 60 L/min) and 8 mL/kg (decelerating flow 40 L/min). There was no correlation between comfort and systolic blood pressure, heart rate, or respiratory rate. Ventilator parameters may impact patients' comfort substantially. Future studies may help identify evidence-based methodology for gauging comfort following changes in ventilator settings and the settings that are most likely to positively impact various groups of patients

Low FVC/TLC in Preserved Ratio Impaired Spirometry (PRISm) is associated with features of and progression to obstructive lung disease.

One quarter of individuals with Preserved Ratio Impaired Spirometry (PRISm) will develop airflow obstruction, but there are no established methods to identify these individuals. We examined the utility of FVC/TLC in identifying features of obstructive lung disease. The ratio of post-bronchodilator FVC and TLCCT from chest CT (FVC/TLCCT) among current and former smokers with PRISm (FEV1/FVC ≥ 0.7 and FEV1 &lt; 80%) in COPDGene was used to stratify subjects into quartiles: very high, high, low, and very low. We examined the associations between FVC/TLCCT quartiles and (1) baseline characteristics, (2) respiratory exacerbations, (3) progression to COPD at 5 years, and (4) all-cause mortality. Among participants with PRISm at baseline (n = 1,131), the very low FVC/TLCCT quartile was associated with increased gas trapping and emphysema, and higher rates of progression to COPD at 5 years (36% versus 17%; p &lt; 0.001) relative to the very high quartile. The very low FVC/TLCCT quartile was associated with increased total (IRR = 1.65; 95% CI [1.07-2.54]) and severe (IRR = 2.24; 95% CI [1.29-3.89]) respiratory exacerbations. Mortality was lower in the very high FVC/TLCCT quartile relative to the other quartiles combined. Reduced FVC/TLCCT ratio in PRISm is associated with increased symptoms, radiographic emphysema and gas trapping, exacerbations, and progression to COPD

NAC reduces oxidative injury.

<p>To determine the mechanism behind distal organ injury, mice were pretreated intraperitoneally with, N-acetyl-cysteine (NAC). <b><i>A</i></b>, Compared to mice given vehicle control (No-NAC), NAC treated mice had significantly lower plasma I-FABP after 2 h of intestinal ischemia. <b><i>B</i></b>, NAC also affected defensins at 1 h ischemia, though no significance was achieved. <b><i>C</i></b>, MPO activity of lung homogenates illustrated a significant reduction in mice that were treated with NAC compared to vehicle controls (No-NAC) at 1 h ischemia. <b><i>D</i></b>, There was also significant reduction in TNF-α cytokine in lung homogenates after NAC treatment at 1 h ischemia. <b><i>E</i></b>, At 2 h ischemia, there was slight reduction in IL-1β in the NAC treated mice compared to vehicle controls, though significance was not achieved probably due to the short half-life of NAC. (n = 3 for shams, n = 4 for both No-NAC and NAC) ^#<i>p<0.05</i> compared to vehicle (No-NAC) treated mice.</p