Exertional Desaturation in Idiopathic Pulmonary Fibrosis: The Role of Oxygen Supplementation in Modifying Cerebral-Skeletal Muscle Oxygenation and Systemic Hemodynamics.

BACKGROUND: In patients with idiopathic pulmonary fibrosis (IPF) with isolated exertional desaturation, there are limited data regarding the effectiveness of oxygen supplementation during exercise training; the underlying mechanisms that contribute to these responses are unknown. OBJECTIVES: To examine in these IPF patients the effects of oxygen supplementation during submaximal exercise (vs. medical air) on cerebral/skeletal muscle oxygenation and systemic hemodynamics. METHODS: In this randomized, cross-over, placebo-controlled trial, IPF patients (n = 13; 63.4 ± 9.6 years) without resting hypoxemia but a significant desaturation during maximal cardiopulmonary exercise testing underwent 2 steady-state exercise trials (65% peak-work-load), breathing either oxygen-enriched or medical air. Cerebral/skeletal muscle oxygenation (near-infrared spectroscopy) and beat-by-beat hemodynamics (photoplethysmography) were monitored. RESULTS: In the air protocol, from the initial minutes of submaximal exercise, patients exhibited a marked decline in cerebral oxygenated hemoglobin (O2Hb) and an abrupt rise in deoxygenated hemoglobin (HHb). Oxygen supplementation alleviated desaturation, lessened dyspnea, and prolonged exercise duration (p < 0.01). Oxygen supplementation during exercise (i) attenuated cerebral deoxygenation (cerebral-HHb: 0.7 ± 1.9 vs. 2.5 ± 1.5 µmol/L, O2 and air protocol; p = 0.009) and prevented cerebral-Hbdifference decline (2.1 ± 2.7 vs. -1.7 ± 2.0 µmol/L; p = 0.001), (ii) lessened the decline in muscle O2-saturation index, and (iii) at isotime exercise, it resulted in lower muscle-HHb (p = 0.05) and less leg fatigue (p < 0.05). No differences between protocols were observed in exercise cardiac output and vascular resistance. CONCLUSIONS: IPF patients with isolated exertional hypoxemia exhibit an inability to increase/maintain cerebral oxygenation during submaximal exercise. Correcting desaturation with O2 supplementation prevented the decline in brain oxygenation, improved muscle oxygenation, and lessened dyspnea, suggesting an efficacy of acute oxygen supplementation during exercise training in protecting brain hypoxia in these IPF patients.

Changes in the respiratory function of COVID-19 survivors during follow-up: A novel respiratory disorder on the rise?

BACKGROUND: The Human Coronavirus Disease 2019 (COVID-19) is a highly contagious respiratory disorder that may result in acute respiratory distress syndrome. The aim of this review was to investigate the incidence and type of respiratory function abnormalities during the follow-up of patients who recovered from COVID-19. METHODS: A systematic search of MEDLINE was conducted, utilising various term combinations. Studies that assessed any respiratory function parameter during the re-evaluation of patients who recovered from COVID-19 and were published as full-text articles in English are included in this review. RESULTS: Amongst 183 articles initially retrieved, 8 fulfilled the criteria and were included in this review; they involved a total of 341 adult patients. Four were retrospective studies, one was a prospective cohort study, one was a randomised control trial and two were case reports/case series. The follow-up time ranged from 1 month since symptom onset to 3 months after discharge. The most frequent abnormality was reduced lung diffusion for carbon monoxide (DLCO), followed by a restrictive pattern. Other findings are the lack of resting hypoxemia, the reduced respiratory muscle strength and the decreased exercise capacity, although relative data are extremely limited. CONCLUSION: Patients who recovered from COVID-19 present with abnormal respiratory function at short-term follow-up, mainly with reduced lung diffusion and a restrictive pattern. However, results are currently very limited in order safe conclusions to be made, regarding the exact incidence of these abnormalities and whether they may be temporary or permanent.

Pulmonary rehabilitation for cystic fibrosis: A narrative review of current literature.

Pulmonary rehabilitation is a key component in cystic fibrosis care.  This review summarizes the recent evidence in the area of pulmonary rehabilitation for cystic fibrosis in the form of questions and answers regarding interventions, indications, benefits and risks of pulmonary rehabilitation. Pulmonary rehabilitation includes airway clearance techniques, exercise training, education and behaviour change and can improve patients' exercise capacity, muscle strength, quality of life and nutritional status. Airway clearance techniques have beneficial effects for clearing mucous. Over the past years, evidence for the beneficial effects of exercise training on exercise capacity and overall lung health is growing. In cystic fibrosis, multiple factors result in reduced exercise capacity. All modalities of pulmonary rehabilitation should be offered to patients with cystic fibrosis, as the benefits in most cases outweigh the risks, though the optimal regimens need to be yet defined.

Moxifloxacin in Chronic Obstructive Pulmonary Disease: Pharmacokinetics and Penetration into Bronchial Secretions in Ward and Intensive Care Unit Patients.

This study aimed to evaluate the pharmacokinetic profile of moxifloxacin (MXF) in serum and sputum/bronchial secretions of 22 patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) hospitalized in the ward and intensive care unit (ICU). The data showed that ICU patients had lower concentrations in secretions (P = 0.01). However, no other statistically significant differences were observed in pharmacokinetic parameters and penetration in secretions between ward and ICU patients. MXF showed a favorable pharmacokinetic profile, and the pharmacodynamic targets for common pathogens for AECOPD were achieved.

Phenotyping Exercise Limitation in Systemic Sclerosis: The Use of Cardiopulmonary Exercise Testing.

BACKGROUND: Exercise impairment is a common symptom of systemic sclerosis (SSc), a disorder which is frequently complicated by cardiopulmonary involvement. OBJECTIVES: This study's aims were: (a) to define the prevalence and the potential causes of limited exercise capacity and (b) to study potential differences in clinical, radiological and functional characteristics and blood serology among SSc patients with exercise limitation of different etiology. METHODS: Prospectively collected data on SSc patients who had conducted full lung function testing, blood serology, thorax high-resolution computed tomography, Doppler echocardiogram and a maximal cardiopulmonary exercise testing (CPET) were retrospectively analyzed. Using a CPET algorithm, patients were characterized as having normal or subnormal exercise capacity (N), respiratory limitation (RL), left ventricular dysfunction (LVD) or pulmonary vasculopathy (PV). Group comparisons were conducted using either one-way ANOVA or the Kruskal-Wallis test. A p value <0.05 was considered significant. RESULTS: The study population consisted of 78 patients (53.7 ± 13.7 years old; 10.3% male). PV was present in 32.1%, LVD in 25.6% and RL in 10.2%, while 32.1% of the patients constituted the N group. The presence of antisclero-70 antibodies, low anaerobic threshold and low peak exercise capacity measures could discriminate LVD from the other groups. Low end-tidal carbon dioxide pressure and its change from rest to anaerobic threshold could discriminate between the PV, LVD and N groups, while respiratory restriction along with ventilatory inefficiency indices could differentiate the RL group from the rest. CONCLUSIONS: The combined evaluation of CPET gas exchange patterns with baseline measurements could discriminate the causes of exercise limitation among SSc patients.

Resting energy expenditure in OSAS: the impact of a single CPAP application.

PURPOSE: Data on the impact of obstructive sleep apnea syndrome (OSAS) and its treatment on resting energy expenditure (REE) are currently few and conflicting. The purpose of the present study was to investigate the impact of OSAS on REE, as measured before and after sleep, and the changes in REE after a single continuous positive airway pressure (CPAP) application, for the first time in literature. METHODS: This is a nested case-control study. From the initial study population, two groups were formed, based on the results of nocturnal polysomnography: a group of male OSAS patients and a group of male, age-matched non-OSAS controls. REE was measured in both groups before and after sleep by indirect calorimetry, while patients repeated REE measurements before and after a single nasal CPAP application. RESULTS: Ninety-two male OSAS patients (45.3 ± 12.8 years old) and 19 male non-OSAS controls (50.8 ± 11.7 years old) were studied. REE/lean body mass (LBM) was higher among patients compared to controls both pre- (29.6 ± 12 vs 22.9 ± 7.9 kcal/kg; p = 0.022, correspondingly) and post-sleep (26.4 ± 9.6 vs 21.6 ± 9 kcal/kg; p = 0.047 correspondingly). REE/LBM decreased significantly after sleep in OSAS patients (p = 0.002), but not in controls; this difference was most evident among patients with more severe disease and higher desaturation. A single nasal CPAP application diminished the pre-post REE/LBM difference (30.3 ± 8.2 vs 28.3 ± 10.3 kcal/kg; p = 0.265), but only among responders. CONCLUSIONS: In OSAS patients, REE values are high and vary significantly before and after sleep. A single nasal CPAP application diminishes this difference among responders, possibly through reversal of nocturnal desaturation.

Moxifloxacin pharmacokinetics and pleural fluid penetration in patients with pleural effusion.

The aim of this study was to evaluate the pharmacokinetics and penetration of moxifloxacin (MXF) in patients with various types of pleural effusion. Twelve patients with empyema/parapneumonic effusion (PPE) and 12 patients with malignant pleural effusion were enrolled in the study. A single-dose pharmacokinetic study was performed after intravenous administration of 400 mg MXF. Serial plasma (PL) and pleural fluid (PF) samples were collected during a 24-h time interval after drug administration. The MXF concentration in PL and PF was determined by high-performance liquid chromatography, and main pharmacokinetic parameters were estimated. Penetration of MXF in PF was determined by the ratio of the area under the concentration-time curve from time zero to 24 h (AUC24) in PF (AUC24PF) to the AUC24 in PL. No statistically significant differences in the pharmacokinetics in PL were observed between the two groups, despite the large interindividual variability in the volume of distribution, clearance, and elimination half-life. The maximum concentration in PF (CmaxPF) in patients with empyema/PPE was 2.23±1.31 mg/liter, and it was detected 7.50±2.39 h after the initiation of the infusion. In patients with malignant effusion, CmaxPF was 2.96±1.45 mg/liter, but it was observed significantly earlier, at 3.58±1.38 h (P<0.001). Both groups revealed similar values of AUC24PF (31.83±23.52 versus 32.81±12.66 mg·h/liter). Penetration of MXF into PF was similarly good in both patient groups (1.11±0.74 versus 1.17±0.39). Despite similar plasma pharmacokinetics, patients with empyema/parapneumonic effusion showed a significant delay in achievement of PF maximum MXF levels compared to those with malignant effusion. However, in both groups, the degree of MXF PF penetration and the on-site drug exposure, expressed by AUC24PF, did not differ according to the type of pleural effusion.

COPD assessment test: a simple tool to evaluate disease severity and response to treatment.

The COPD assessment test (CAT) is a short questionnaire designed to assess the impairment in health status of COPD patients. We aimed to determine the change of the CAT in COPD patients after 1 year of treatment and test the association between the score and clinical and lung function variables. Methods A cohort of 111 newly diagnosed COPD patients in primary care was evaluated at baseline and one year after the implementation of the recommended treatment according to the Global Initiative for the management of COPD (GOLD). Results Most of the patients (82%) were diagnosed with mild to moderate airflow limitation (mean FEV1 72 ± 21.5% predicted) and the CAT score increased in proportion with the GOLD stage of severity. The CAT significantly correlated with the number of exacerbations, visits to general practitioners and days of hospitalization both at the beginning and at 1 year follow-up. A strong negative correlation between the CAT score and FEV1 predicted was also observed. The CAT was responsive to the application of treatment with a significant improvement in the mean score (95% confidence interval) following 12 months of treatment by -2.4 (-2.9, -1.9) despite the small decline in lung function indices. The number of exacerbations in the preceding year and FEV1 were independent predictors of the CAT score in the general linear model. Conclusion The CAT questionnaire may serve as a simple, measurable tool complementary to spirometry in the assessment of severity and of response to treatment in unselected COPD patients in primary care.

Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. From In vitro to In vivo.

Background: Pulmonary hypertension is common symptom among several diseases. The consequences are severe for several organs. Pulmonary hypertension is usually under-diagnosed and the main symptom observed is dyspnea with or without exercise. Currently we have several treatment modalities administered orally, via inhalation, intravenously and subcutaneously. In advanced disease then heart or lung transplantation is considered. The objective of the study was to investigate the optimum method of aerosol production for the drugs: iloprost, paclitaxel and the novel sotatercept. Materials and Methods: In our experiment we used the drugs iloprost, paclitaxel and the novel sotatercept, in an experimental concept of nebulization. We performed nebulization experiments with 3 jet nebulizers and 3 ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5µm in mass median aerodynamic diameter. Results: We concluded that paclitaxel cannot produce small droplets and is also still very greasy and possible dangerous for alveoli. However; iloprost vs sotatercept had smaller droplet size formation at both inhaled technologies (1.37<2.23 and 1.92<3.11, jet and ultrasound respectively). Moreover; residual cup designs C and G create the smallest droplet size in both iloprost and sotatercept. There was no difference for the droplet formation between the facemask and cone mouthpieces. Discussion: Iloprost and sotatercept can be administered as aerosol in any type of nebulisation system and they are both efficient with the residual cups loaded with small doses of the drug (2.08 and 2.12 accordingly).

The financial crisis has an impact in sleep medicine: experience of a sleep clinic in Greece.

OBJECTIVE: Greece has entered a long period of economic crisis with adverse effects in daily life. The aim of our study was to evaluate the impact of the economic crisis on the population visiting a sleep clinic between years 2008 and 2011. METHODS: Comparison of the number of patients, anthropometric data, symptoms, and treatment between 2008 (beginning of crisis) to 2011(great impact of crisis) was conducted. RESULTS: The number of patients significantly reduced in 2011(n = 127) compared with that in 2008 (n = 463) and 2009 (n = 465). The mean age, body mass index, and Epworth Sleepiness Scale did not differ between the years (52.2 ± 13.7 years, 33 ± 7.4 kg/m(2), and 11.4 ± 5.4, respectively). The main symptom of the patients was daytime sleepiness, and the symptoms that worsened in 2011 compared with 2008 were headaches (32.4 vs. 49.6 %, p < 0.001) and nightmares (44 vs. 75.9 %, p < 0.001). In 2008, 69.1 % of patients required treatment for obstructive sleep apnea syndrome with continuous positive airway pressure (CPAP), and 81.6 % of them received CPAP. In 2011, 67.7 % required treatment, but only 52.3 % received CPAP. CONCLUSIONS: The economic crisis can be reflected in the number of patients, their symptoms and their treatment options.

Lemierre's syndrome presenting to the ED: rapidly fatal sepsis caused by methicillin-susceptible Staphylococcus aureus Staphylococcus protein A type t044.

We describe the case of a fatal septic illness in a previously healthy young man caused by community-acquired methicillin-susceptible Staphylococcus aureus of Staphylococcus protein A (spa) type t044. The patient developed a devastating Lemierre-like syndrome with extensive thrombosis of inferior vena cava and iliac veins with multiple metastatic septic emboli of the lungs. He presented to the emergency department with rapidly progressing sepsis followed by multiple organ dysfunction syndrome. Recognition of such virulent community-acquired strains is of great importance because they could prove to be emerging pathogens for life-threatening diseases.

Repeated episodes of respiratory failure due to bilateral vocal cord paralysis.

BACKGROUND: Bilateral vocal cord paralysis can produce severe airway obstruction, leading to acute respiratory failure. Discriminating the pathology of the upper airway from chronic obstructive diseases of the lower airways often presents a challenge for clinicians in the Emergency Department. OBJECTIVES: To underlie the value of clinical examination and flow-volume loops in the establishment of diagnosis of upper airway obstruction. CASE REPORT: We describe the case of a 55-year-old female ex-smoker who presented with a long history of hoarseness and progressive exertional dyspnea. The patient developed repeated episodes of acute respiratory failure and was supported with noninvasive ventilation. The diagnosis of bilateral vocal cord paralysis was finally established by patient's symptoms and flow-volume loops demonstrating variable extrathoracic obstruction. CONCLUSION: Vocal cord paralysis is a rare and often neglected condition, contributing to repeated episodes of acute respiratory failure. Flow-volume loop is a useful tool when symptoms are suggestive of upper airway obstruction.

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.

Tigecycline Pharmacokinetic and Pharmacodynamic Profile in Patients with Chronic Obstructive Pulmonary Disease Exacerbation.

BACKGROUND: We aimed to evaluate the pharmacokinetic profile of tigecycline in plasma and its penetration to sputum in moderately ill patients with an infectious acute exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: Eleven patients hospitalized with acute respiratory failure due to an acute COPD exacerbation with clinical evidence of an infectious cause received tigecycline 50 mg twice daily after an initial loading dose of 100 mg. Blood and sputum samples were collected at steady state after dose seven. RESULTS: In plasma, mean Cmax pl was 975.95 ± 490.36 ng/mL and mean Cmin pl was 214.48 ±140.62 ng/mL. In sputum, mean Cmax sp was 641.91 ± 253.07 ng/mL and mean Cmin sp was 308.06 ± 61.7 ng/mL. In plasma, mean AUC 0-12 pl was 3765.89 ± 1862.23 ng*h/mL, while in sputum mean AUC 0-12 sp was 4023.27 ± 793.37 ng*h/mL. The mean penetration ratio for the 10/11 patients was 1.65 ± 1.35. The mean Free AUC0-24 pl/MIC ratio for Streptococcus pneumoniae and Haemophilus influenzae was 25.10 ± 12.42 and 6.02 ± 2.97, respectively. CONCLUSIONS: Our findings support the clinical effectiveness of tigecycline against commonly causative bacteria in COPD exacerbations and highlight its sufficient lung penetration in pulmonary infections of moderate severity.

COVID-19-Associated Pulmonary Aspergillosis (CAPA) in Northern Greece during 2020-2022: A Comparative Study According to the Main Consensus Criteria and Definitions.

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) has emerged as an important complication among patients with acute respiratory failure due to SARS-CoV-2 infection. Almost 2.5 years since the start of the COVID-19 pandemic, it continues to raise concerns as an extra factor that contributes to increased mortality, which is mostly because its diagnosis and management remain challenging. The present study utilises the cases of forty-three patients hospitalised between August 2020 and February 2022 whose information was gathered from ten ICUs and special care units based in northern Greece. The main aim was to describe the gained experience in diagnosing CAPA, according to the implementation of the main existing diagnostic consensus criteria and definitions, and present the different classification of the clinical cases due to the alternative algorithms.

SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial.

Despite advances, few therapeutics have shown efficacy in severe coronavirus disease 2019 (COVID-19). In a different context, virus-specific T cells have proven safe and effective. We conducted a randomized (2:1), open-label, phase 1/2 trial to evaluate the safety and efficacy of off-the-shelf, partially human leukocyte antigen (HLA)-matched, convalescent donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells (CoV-2-STs) in combination with standard of care (SoC) in patients with severe COVID-19 compared to SoC during Delta variant predominance. After a dose-escalated phase 1 safety study, 90 participants were randomized to receive CoV-2-ST+SoC (n = 60) or SoC only (n = 30). The co-primary objectives of the study were the composite of time to recovery and 30-d recovery rate and the in vivo expansion of CoV-2-STs in patients receiving CoV-2-ST+SoC over SoC. The key secondary objective was survival on day 60. CoV-2-ST+SoC treatment was safe and well tolerated. The study met the primary composite endpoint (CoV-2-ST+SoC versus SoC: recovery rate 65% versus 38%, P = 0.017; median recovery time 11 d versus not reached, P = 0.052, respectively; rate ratio for recovery 1.71 (95% confidence interval 1.03-2.83, P = 0.036)) and the co-primary objective of significant CoV-2-ST expansion compared to SοC (CoV-2-ST+SoC versus SoC, P = 0.047). Overall, in hospitalized patients with severe COVID-19, adoptive immunotherapy with CoV-2-STs was feasible and safe. Larger trials are needed to strengthen the preliminary evidence of clinical benefit in severe COVID-19. EudraCT identifier: 2021-001022-22 .

Saliva and blood concentration of cefuroxime in patients undergoing maxillofacial surgery.

PURPOSE: To investigate the penetration of cefuroxime into the parotid saliva after short-term intravenous administration in patients undergoing various maxillofacial surgical procedures. PATIENTS AND METHODS: A total of 12 patients, 10 males and 2 females, with a mean age of 41 ± 21.2 years, participated in the present study. Each patient received 1.5 g of intravenous cefuroxime every 8 hours. Blood and parotid saliva samples were collected concomitantly, on the third day of therapy, just before the infusion of the first morning dose, and 0.5 hour after its end. All samples were analyzed using high-performance liquid chromatography. RESULTS: The cefuroxime concentration in plasma and saliva before infusion was 2.08 ± 1.05 mg/L and 0.46 ± 0.33 mg/L, respectively. At 30 minutes after the end of infusion, the corresponding concentrations were 55.54 ± 20.24 mg/L and 14.50 ± 7.85 mg/L. The saliva/plasma ratio was 0.25 ± 0.18 before and 0.26 ± 0.12 after the infusion. CONCLUSIONS: Cefuroxime is excreted in saliva in high levels shortly after infusion but is detected in far lower levels 8 hours after infusion. Taking into consideration the minimum inhibitory concentration values of common pathogens, we have concluded that the saliva concentrations of the drug are sufficient against some, but not all, pathogens involved in the oral-maxillofacial area.