Long COVID-19 Pulmonary Sequelae and Management Considerations

The human coronavirus 2019 disease (COVID-19) and the associated acute respiratory distress syndrome (ARDS) are responsible for the worst global health crisis of the last century. Similarly, to previous coronaviruses leading to past pandemics, including severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS), a growing body of evidence support that a substantial minority of patients surviving the acute phase of the disease present with long-term sequelae lasting for up to 6 months following acute infection. The clinical spectrum of these manifestations is widespread across multiple organs and consists of the long-COVID-19 syndrome. The aim of the current review is to summarize the current state of knowledge on the pulmonary manifestations of the long COVID-19 syndrome including clinical symptoms, parenchymal, and functional abnormalities, as well as highlight epidemiology, risk factors, and follow-up strategies for early identification and timely therapeutic interventions. The literature data on management considerations including the role of corticosteroids and antifibrotic treatment, as well as the therapeutic potential of a structured and personalized pulmonary rehabilitation program are detailed and discussed

Diagnosis and management of combined post- and precapillary pulmonary hypertension in a patient with multiple comorbidities

Diagnosis of pulmonary hypertension requires a laborious investigation that must be performed in accordance with international guidelines. Right-heart catheterization is the gold standard examination to assess the degree of hemodynamic impairment of  post- or precapillary origin, guiding management. The presence of comorbidities is becoming rather frequent in real-life pulmonary hypertension cases, thus creating diagnostic and therapeutic complexity. We present a case of combined post- and precapillary pulmonary hypertension in a patient with ischemic heart disease and combined pulmonary fibrosis and emphysema, in order to describe the diagnostic algorithm for pulmonary hypertension and elucidate the problematic aspects of managing this debilitating disease in a patient with several comorbidities. Current guidelines do not support the use of specific vasodilator treatment in group II — due to heart disease and group III-due to lung disease pulmonary hypertension, unless the patient presents with severe pulmonary hypertension (mean pulmonary artery pressure > 35 mm Hg or cardiac index < 2.0 L/min) with right ventricular dysfunction and is treated in an expert center and preferably in the context of a randomized control trial. In the case presented, therapeutic management focused, firstly, on treatment of the underlying heart and lung disease and, subsequently, on specific vasoactive therapy, due to severe hemodynamic deterioration

Longitudinal changes in exercise capacity among adult cystic fibrosis patients

Introduction: Longitudinal data regarding changes in exercise capacity among adult cystic fibrosis (CF) patients are currently scarce. The aim of this brief report was to assess changes in exercise capacity among adult CF patients with stable and mild-to-moderate disease eight years after their initial evaluation.Material and methods: Maximum cardiopulmonary exercise testing (CPET) was utilized. Other assessments included Doppler echocardiography, the 6-minute walking test, spirometry, and lung volume evaluation. Results: Eleven (6 male, 5 female) patients completed both evaluations (initial and after eight years). During follow-up, indices of ventilatory impairment (such as ventilatory reserve; p=0.019, and ventilatory equivalent for carbon dioxide; p = 0.047) deterio-rated significantly following a decline in respiratory function measurements. Peak oxygen uptake (VO2), both as an absolute (26.6 ± 8.46 vs 23.89 ± 6.16 mL/kg/min; p = 0.098) and as a % of predicted value (71.21 ± 16.54 vs 70.60 ± 15.45; p = 0.872), did not deteriorate. This is also true for oxygen pulse (p = 0.743), left heart ejection fraction (p = 0.574), and pulmonary artery systolic pressure (p = 0.441). However, the anaerobic threshold, both as an absolute (p = 0.009) and as a % of predicted value (p = 0.047), was significantly lower during follow-up. Conclusion: In adult CF patients with stable, mild-to-moderate disease, a peak VO2 may be preserved for several years. However, even in these patients, deconditioning is present

The Impact of Homogeneous Versus Heterogeneous Emphysema on Dynamic Hyperinflation in Patients With Severe COPD Assessed for Lung Volume Reduction

Dynamic hyperinflation (DH) is a pathophysiologic hallmark of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to investigate the impact of emphysema distribution on DH during a maximal cardiopulmonary exercise test (CPET) in patients with severe COPD. This was a retrospective analysis of prospectively collected data among severe COPD patients who underwent thoracic high-resolution computed tomography, full lung function measurements and maximal CPET with inspiratory manouvers as assessment for a lung volume reduction procedure. ΔIC was calculated by subtracting the end-exercise inspiratory capacity (eIC) from resting IC (rIC) and expressed as a percentage of rIC (ΔIC %). Emphysema quantification was conducted at 3 predefined levels using the syngo PULMO-CT (Siemens AG); a difference >25% between best and worse slice was defined as heterogeneous emphysema. Fifty patients with heterogeneous (62.7% male; 60.9 ± 7.5 years old; FEV(1)% = 32.4 ± 11.4) and 14 with homogeneous emphysema (61.5% male; 62.5 ± 5.9 years old; FEV(1)% = 28.1 ± 10.3) fulfilled the enrolment criteria. The groups were matched for all baseline variables. ΔIC% was significantly higher in homogeneous emphysema (39.8% ± 9.8% vs.31.2% ± 13%, p = 0.031), while no other CPET parameter differed between the groups. Upper lobe predominance of emphysema correlated positively with peak oxygen pulse, peak oxygen uptake and peak respiratory rate, and negatively with ΔIC%. Homogeneous emphysema is associated with more DH during maximum exercise in COPD patients

Clinical impact of anemia of chronic disease among chronic obstructive pulmonary disease patients

Introduction: Anemia of chronic disease (ACD) is a disorder occurring in subjects with chronic immune activation. Chronic Obstructive Pulmonary Disease (COPD) is characterized by systemic inflammation, so it could be accompanied by ACD. Aim: The aim of the study was: a) to determine the prevalence of ACD among stable COPD patients, b) to investigate the potential differences in exercise capacity, utilising cardiopulmonary exercise testing between patients with ACD and COPD (cases) and matched controls (patients with COPD without ACD) and c) to investigate the potential differences in the concentration of C-reactive protein, interleukin-1b, interleukin-6, interleukin-10, tumor necrosis factor-a, interferon-γ and erythropoietin between these two groups, for the first time in literature. Methods: The initial study population consisted of consecutive clinically stable patients with COPD (post bronchodilation FEV₁/FVC30ng/ml, c) total binding iron capacity30 ng/ml, σιδηροδεσμευτική ικανότητα ορού <250 mg/dl, και κορεσμό τρανσφερρίνης μεταξύ 15-50%. Οι ασθενείς αυτοί (cases) καθώς και ισάριθμοι «μάρτυρες» (controls) (ασθενείς με σταθερή ΧΑΠ ταυτισμένοι ως προς την ηλικία, το φύλο, το ύψος, την FEV₁ και την καπνιστική συνήθεια) υπεβλήθησαν στη συνέχεια σε προσδιορισμό φλεγμονωδών παραμέτρων και ερυθροποιητίνης και σε μέγιστη καρδιοαναπνευστική δοκιμασία κόπωσης. Αποτελέσματα: Από τους 1171 ασθενείς των εξωτερικών ιατρείων, οι 283 (79% άντρες, 21% γυναίκες) παρουσίαζαν σταθερή ΧΑΠ. Από αυτούς 10,24% παρουσίαζε ΑΧΝ (27 άντρες, 2 γυναίκες), η οποία ήταν ήπια. Συγκριτικά με τους μάρτυρες, οι ασθενείς είχαν: α) μικρότερη μέγιστη πρόσληψη οξυγόνου, β) μικρότερο απόλυτο έργο, γ) μικρότερο % προβλεπόμενο έργο, δ) χαμηλότερο παλμό οξυγόνου και ε) χαμηλότερο % προβλεπόμενο παλμό οξυγόνου, ενώ υπήρχε τάση για χαμηλότερο % προβλεπόμενο αναερόβιο κατώφλι (p=0,062). Επιπλέον οι ασθενείς είχαν υψηλότερη συγκέντρωση ιντερφερόνης-γ, ιντερλευκίνης-10 και ερυθροποιητίνης ορού σε σύγκριση με τους μάρτυρες. Συμπέρασμα: Η ΑΧΝ συνοδεύει συχνά την ΧΑΠ και μπορεί, πιθανώς, να θεωρηθεί μια ακόμα συστηματική επιπλοκή της. Η παρουσία της ΑΧΝ επηρεάζει σημαντικά την ικανότητα για άσκηση των ασθενών με ΧΑΠ, ενώ είναι πιθανόν η εκδήλωσή της να συσχετίζεται με την παρουσία αντίστασης στη δράση της ερυθροποιητίνης

Cardiotoxicity of Azithromycin in COVID-19: An Overall Proportion Meta-Analysis

Introduction: To explore the incidence of pro-arrhythmic effects such as corrected QT interval (QTc) prolongation, arrhythmic events and myocardial injury of azithromycin as administered for the treatment of COVID-19. Material and Methods: We searched PubMed, the Cochrane Library and Web of Science databases from inception to 18 January 2021, as well as the medRχiv preprint database from 1 August 2020 to 18 January 2021, for studies exploring the cardiotoxicity effects of azithromycin, with or without concomitant use of hydroxychloroquine, in the context of COVID-19. We performed a random effects single-arm meta-analysis of studies to calculate pooled proportion estimates for pro-arrhythmic effects. Meta-regression analyses were conducted to explain between-study heterogeneity. Results: Thirty-four studies with a total of 3088 patients were included. Among 12 studies, the incidence of &gt;60 ms QTc prolongation from baseline was 13% (95% CI 9%–18%, I² = 73%), whereas, among 28 studies, the incidence of QTc ≥ 500 ms at follow-up was 8% (95% CI 6%–11%, I² = 78%). Still, the discontinuation rate due to QTc prolongation was only 3% (95% CI 2%–5%, I² = 55%). The absolute risk of Torsade de pointes and ventricular tachycardia was 0.2% and 0.8%, respectively. Increased age, male sex, presence of hypertension or diabetes mellitus, use of QTc prolonging medication, prolonged baseline QTc interval and indicators of disease severity such as death explained between-study heterogeneity. Conclusions: Azithromycin, with or without hydroxychloroquine, leads to a significant risk for critical QTc prolongation in patients with COVID-19. Due to its cardiotoxicity effects and its unproven efficacy in Covid19, azithromycin use should be limited to cases of bacterial co-infection

Cardiotoxicity of azithromycin in COVID-19: an overall proportion meta-analysis

Introduction: To explore the incidence of pro-arrhythmic effects such as corrected QT interval (QTc) prolongation, arrhythmic events and myocardial injury of azithromycin as administered for the treatment of COVID-19. Material and methods: We searched PubMed, the Cochrane Library and Web of Science databases from inception to 18 January 2021, as well as the medRχiv preprint database from 1 August 2020 to 18 January 2021, for studies exploring the cardiotoxicity effects of azithromycin, with or without concomitant use of hydroxychloroquine, in the context of Covid19. We performed a random effects single-arm meta-analysis of studies to calculate pooled proportion estimates for pro-arrhythmic effects. Meta-regression analyses were conducted to explain between-study heterogeneity. Results: Thirty-four studies with a total of 3088 patients were included. Among 12 studies, the incidence of &gt; 60ms QTc prolongation from baseline was 13% (95% CI 9%–18%, I2 = 73%), whereas, among 28 studies, the incidence of QTc ≥ 500 ms at follow-up was 8% (95% CI 6%–11%, I2 = 78%). Still, the discontinuation rate due to QTc prolongation was only 3% (95% CI 2%–5%, I2 = 55%). The absolute risk of Torsade de pointes and ventricular tachycardia was 0.2% and 0.8%, respectively. Increased age, male sex, presence of hypertension or diabetes mellitus, use of QTc prolonging medication, prolonged baseline QTc interval and indicators of disease severity such as death explained between-study heterogeneity. Conclusions: Azithromycin, with or without hydroxychloroquine, leads to a significant risk for critical QTc prolongation in patients with Covid19. Due to its cardiotoxicity effects and its unproven efficacy in Covid19, azithromycin use should be limited to cases of bacterial co-infection

Efficacy and Safety of Nintedanib in Patients with Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD): A Real-World Single Center Experience

Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) is a severe and fatal manifestation of systemic autoimmune disorders. Therapies rely on immunomodulators but their efficacy in ILD progression remains uncertain. Nintedanib, an antifibrotic agent that slows pulmonary function decline, has been approved for CTD-ILD treatment. The aim of this study was to assess the effectiveness and safety of nintedanib in CTD-ILD patients in a real-world data setting. A single-center, retrospective, and descriptive analysis of CTD-ILD patients treated with nintedanib from June 2019 to November 2022 was performed. The assessment of nintedanib treatment’s efficacy was judged solely on the evolution of pulmonary function tests (PFTs), which were evaluated before and after treatment. Twenty-one patients (67% females, median age 64 years (IQR = 9) with CTD-ILD (systemic sclerosis n = 9, rheumatoid arthritis n = 5, dermatomyositis n = 4, juvenile rheumatoid arthritis n = 1, undifferentiated CTD n = 1, interstitial pneumonia with autoimmune features n = 1), 18 of whom were on concomitant immunosuppressives, had a median follow-up period of 10 months (IQR = 5). PFTs before and after treatment did not significantly differ. The mean FVC% difference was +0.9 (sd = 7.6) and the mean DLco% difference was +3.4 (sd = 12.6), suggesting numerical improvement of PFTs. The average percentage change was −0.3% and +7.6% for FVC% and DLco%, respectively, indicating stabilization of lung function. Our real-world data across a broad spectrum of CTD-ILD suggest that nintedanib could be beneficial in combination with immunosuppressives in slowing the rate of lung function decline