Impaired Cardiovascular Response to Exercise in Patients with Severe Asthma: A Case-Control Study.

Background: Although asthmatics may present reduced exercise capacity, data on their cardiovascular responses during exercise testing have been scarcely investigated. The aim of this pilot case-control study is to test: a) whether double product (DP), an index of cardiovascular reserve, differs among patients with severe and mild-moderate asthma, and b) whether DP is associated with asthma control level, physical activity (PA) and exercise capacity, in asthmatics population. Materials and Methods: A group of patients with severe asthma (group S) and a matched group of patients with mild-moderate asthma (group M) was studied. All participants completed asthma control and physical activity (IPAC) questionnaires, lung function measurements and six-minute walk test. The exercise capacity (as 6-minute walk distance (6MWD) and corresponding work), the Borg Dyspnea, the rating of perceived excursion and the average PA METS were recorded. Results: A total of 18 patients were studied. DP at exercise end was significantly lower in group S, compared to group M (16412.2±4732.1 vs. 18594.8±3984.4 mmHgXbpm; p=0.041) and was moderately associated with % predicted 6MWD (r=0.592; p=0.001). Group S patients were also presented with lower moderate intensity PA, compared to group M, while exercise capacity was similar between the groups. Asthma control level had no impact on exercise capacity nor PA parameters. Conclusion: Patients with severe asthma may have impaired cardiovascular reserve as established by DP, even when exercise capacity is indifferent from patients with milder disease. As an easy-to-assess parameter, DP may offer further information in the functional evaluation of these patients.

Molecular Basis of Resistance to First-Line Drugs of Mycobacterium tuberculosis/canettii Strains in Greece.

The aim of this study was to determine the rate and the mutations of genes involved to the first-line antituberculous drugs' resistance of M. tuberculosis/canettii isolated in Central Greece from 2010 to 2019. During the study period, the rate of resistance to isoniazid, rifampicin, ethambutol, and pyrazinamide was 5.4%, 0.4%, 1.1%, and 1.1%, respectively. All phenotypically resistant isolates (14 to isoniazid, 3 to ethambutol, 3 to pyrazinamide, and 1 to rifampicin) and 17 susceptible isolates (control group) were tested for the presence of mutations/alterations/polymorphisms by PCR followed by sequencing analysis. The molecular typing of isolates was based on multispacer sequence typing. Despite the phenotypic resistance, mutations were detected in 13 of 21 isolates (11 isoniazid resistant, 1 rifampicin, and 1 pyrazinamide resistant). Four isoniazid-resistant strains carried the most common mutations S315T and C-15T, whereas the remaining seven isolates carried either less known (E399, A162, W477STOP, S94A, G-48A, C-54T, C-17T, L203, A196, S124, and K367) or novel (D74N, G691S, Ains-85, and D171G); none of the susceptible strains was found to be positive for any novel mutation. The two single rifampicin- and pyrazinamide-resistant strains carried the known mutations S450L (also referred as S531L) and L182W, respectively. The presence of uncommon or novel mutations conferring resistance to isoniazid (INH) creates a diagnostic problem in the routine microbiological laboratory, since commercial methods are focused on the detection of the most common mechanisms of resistance (S315T, C-15T, A-16G, T-8C, and T-8A), therefore, fail to detect such strains. The regional differences in the frequencies of mutations associated with resistance to the first-line drugs provide hints for the development of better molecular-based diagnostic tests.

When there is a pandemic there is no time to waste: should we have hydroxychloroquine in our armoury against COVID-19 infected patients?

The current use of chloroquine and/or hydroxychloroquine, a drug currently used to treat autoimmune rheumatic diseases, in treating severe acute respiratory syndrome caused by coronavirus 2 (SARSCoV-2) or COVID-19-infected patients with pneumonia is a matter of intense consideration. We wish to enter the ongoing debate as to whether this well-known drug must be given to Greek COVID-19-infected patients, especially those with pneumonia. Our arguments are based on the existing data and the capacity of the Greek health system to afford potent anti-viral treatments, which are under immense investigation. We propose several suggestions related to treatment of COVID-19 pneumonia with chloroquine/hydroxychloroquine that we think must be taken into consideration to fit the evolving situation of the pandemic in Greece.

Cardiopulmonary exercise testing in patients with asthma: What is its clinical value?

Asthma is one of the most common respiratory disorders, characterized by fully or largely reversible airflow limitation. Asthma symptoms can be triggered or magnified during exertion, while physical activity limitation is often present among asthmatic patients. Cardiopulmonary exercise testing (CPET) is a dynamic, non-invasive technique which provides a thorough assessment of exercise physiology, involving the integrative assessment of cardiopulmonary, neuromuscular and metabolic responses during exercise. This review summarizes current evidence regarding the utility of CPET in the diagnostic work-up, functional evaluation and therapeutic intervention among patients with asthma, highlighting its potential role for thorough patient assessment and physician clinical desicion-making.

Nasal High Flow Use in COPD Patients with Hypercapnic Respiratory Failure: Treatment Algorithm & Review of the Literature.

Nasal high flow (NHF) therapy has recently gained attention as a new respiratory support system and is increasingly being utilized in every day clinical practice. Recent studies suggest that it may also be effective in patients with hypercapnia and suggest NHF as a possible alternative for patients who cannot tolerate standard noninvasive ventilation. The present review discusses the mechanisms of action that make NHF potentially suitable for chronic obstructive pulmonary disease (COPD) patients and evaluates the current evidence of NHF use for treatment of stable hypercapnic COPD patients as well as acute hypercapnic exacerbation of COPD. An algorithm is also proposed for the clinical application of NHF in patients with acute hypercapnic exacerbation of COPD, based on current literature.

Very preterm neonates receiving "aggressive" nutrition and early nCPAP had similar long-term respiratory outcomes as term neonates.

BACKROUND: The impact of the consistent implementation of "aggressive" nutrition by means of intensive early neonatal nutritional support up to 40-44 weeks postmenstrual age and the use of nasal continuous positive airway pressure (nCPAP) within the first hour of life on the respiratory function of very premature neonates (VPN) at school age is unclear. METHOD: Respiratory function was evaluated in 108 VPN and 70 term controls. Growth, frequency of lower respiratory tract infections, re-hospitalization, and spirometry were recorded up to 8-10 years of age. Comparison was carried out between the two study groups. RESULTS: There was no significant difference in forced expiratory volume in 1 s and forced vital capacity at 8 years of age, and also in lower respiratory tract infections and re-hospitalization due to them, up to 8 years of age between preterm and term neonates. No significant difference was found in spirometry measurements neither between premature neonates with and without BPD nor between the two subgroups of preterms and term neonates. CONCLUSION: "Aggressive" nutrition, persistent nCPAP use, and their impact on early postnatal growth probably positively affect the respiratory function of our study population. These very encouraging results need to be confirmed by larger studies.

Interstitial Lung Disease in Anti-Synthetase Syndrome.

Anti-synthetase syndrome is an autoimmune disorder characterized by the presence of autoantibodies against aminoacyl transfer RNA (tRNA) synthetases, and myositis, interstitial lung disease (ILD), arthritis, fever and Raynaud's phenomenon (RP). We present a 54-year-old woman, who complained of fatigue, low-grade fever, myalgias, arthralgias, RP and dyspnoea on exertion. Chest CT scan revealed features of interstitial lung disease. Due to rapid deterioration of her lung function, she required oxygen support. The patient did not respond to empiric treatment with antibiotics. Autoantibody testing was remarkable for ANA positivity (1/160) and high-titre anti-Jo1 positivity. A diagnosis of anti-synthetase syndrome was made and the patient was placed on high-dose corticosteroids and rituximab with significant improvement. At 1-year follow up, she remains in good condition, without the need for oxygen supplementation.

Application of a One-Dimensional Computational Model for the Prediction of Deposition from a Dry Powder Inhaler.

BACKGROUND: Accurate prediction of the regional deposition of inhaled dry powders as a function of powder properties and breathing pattern is a long-term research goal for pulmonary drug delivery. In the present work, deposition along the respiratory tract of dry powders of Fluticasone propionate and Salmeterol is predicted. METHODS: A one-dimensional particle transport and deposition model is used, whose novelty is in the treatment of the alveolar space of each airway generation as an efficient mixing chamber. This assumption has been supported by simulations and measurements during the last 20 years. The model is applied to two popular pulmonary tree geometries, to investigate the effect of particle size on localized deposition and to estimate the uncertainty due to variations in airway size. RESULTS AND CONCLUSIONS: Application of the model for the specific particle size distribution measured by a cascade impactor in the marketed product ELPENhaler, predicts the whole lung deposition (WLD), as well as the split between pulmonary (PU) and tracheobronchial (TB) deposition. Introduction in the model of modified particle size distributions with increased fractions of fine particles, indicates that the fine-particle dose is a satisfactory predictor of WLD but not of the PU/TB ratio.

Idiopathic pulmonary fibrosis and sleep disorders: no longer strangers in the night.

The prevalence of obstructive sleep apnoea (OSA) is continuously increasing in patients with idiopathic pulmonary fibrosis (IPF) and, for the first time, the recent IPF guidelines recognise OSA as an important associated comorbidity that can affect patient's survival. Thus, it becomes conceivable that clinicians should refer patients with newly diagnosed IPF to sleep centres for the diagnosis and treatment of OSA as well as for addressing issues regarding the reduced compliance of patients with continuous positive airway pressure therapy. The discovery of biomarkers common to both disorders may help early diagnosis, institution of the most appropriate treatment and follow-up of patients. Better understanding of epigenetic changes may provide useful information about pathogenesis and, possibly, development of new drugs for a dismal disease like IPF.

Septic shock due to visceral leishmaniasis, probably transmitted from blood transfusion.

A case of visceral leishmaniasis (VL) in a 77-year-old woman, with renal failure on haemodialysis, admitted in the intensive care unit (ICU) with vascular instability requiring vassopressor treatment, is presented. Initially, no co-infection could be detected. The patient initially responded well when liposomal amphotericin B was administered, after bone marrow demonstrated multiple intra-cellular Leishmania amastigotes and extra-cellular promastigotes. However, the patient died from uncontrolled septic shock from a secondary bacterial infection, the tenth day of admission. To our knowledge, vascular instability has not been reported in VL. Moreover, non-vector transmission was also suspected in this case. The patient had undergone cholecystectomy three months earlier, during which two blood units had been transfused; IgG anti-Leishmania antibodies at a high titer were detected in one of the two healthy blood donors, later.

Anuria due to acute bilateral renal vein occlusion after thrombolysis for pulmonary embolism.

Severe hemorrhage is the more frequent complication of thrombolysis, with intracranial bleeding the most critical one. We report a 73-year-old woman with major pulmonary embolism (PE), yet haemodynamically stable, in whom thrombolysis resulted in severe complications with acute renal failure (ARF) due to bilateral renal vein occlusion, quite unexpected; this complication has never been reported, as yet. We believe that disrupture of peripheral vein clots by thrombolysis led to migration of thrombi particles upwards to the inferior vena cava (IVC) and bilateral renal vein occlusion. However, the large thrombus straddled to the bifurcation of the main pulmonary trunk and extending to the right pulmonary artery, as visualized by transthoracic (TTE) and transesophageal echocardiogram (TEE), was not affected by thrombolysis. Finally, endogenous fibrinolytic activity, under low molecular weight heparin, resulted in a slow dissolution of the pulmonary thrombus and restoration of kidney function.

Hemorrhagic cardiac tamponade in critically ill patients with acute renal failure.

PURPOSE: The purpose of this study was to report the development, management, and follow up of tamponading uremic pericardial effusion in critically ill patients with acute renal failure. SETTING: The setting for this study was an adult, 24-bed tertiary multidisciplinary intensive care unit (ICU) of a university hospital. PATIENTS: The subjects were 5 critically ill patients with multiple organ failure including acute renal failure (ARF) that was slow to resolve. RESULTS: Renal involvement was attributed to renal hypoperfusion, sepsis and myoglobinuria. Continuous veno-venous hemofiltration (CVVH) was instituted early during hospitalization in 4 cases and lasted for 35 to 48 days; renal replacement therapy was not used in 1 case. Tamponade developed late in the course of ARF, after CVVH was discontinued in the 4 cases and was effectively managed with percutaneous pericardiocentesis under echocardiography and continuous catheter drainage of the pericardial sac for 48 to 72 hours. Hemorrhagic fluid (Hb 2.2-5.9 g/dL) with lymphocyte predominance was detected. Transient constrictive-like pericarditis findings were present in all patients after the procedure. All patients were discharged from the hospital in a good condition with normal serum and creatinine levels; 1-year follow up showed a normal echocardiogram. CONCLUSION: Awareness for the possibility of hemorrhagic pericarditis and cardiac tamponade is needed in ICU patients with ARF slow to resolve. Transient constrictive-like pericarditis may present after pericardiocentesis.