Phase angle in assessment and monitoring treatment of individuals with respiratory disease.

Phase angle (PhA) represents a raw variable measured with bioelectrical impedance analysis (BIA) that is used to assess malnutrition in many diseases, including respiratory diseases, mainly chronic obstructive pulmonary disease (COPD). COPD patients with reduced PhA are older, more hypoxic and hypercapnic; patients with more severe COPD have reduced cell mass, evident skeletal muscle depletion, and worsening gas exchange. Malnourished patients with stable COPD in long-term oxygen therapy (LTOT) have more intense dyspnea at rest, greater weight loss over the past 12 months, and more exacerbations per year. Multiple regression analysis highlighted the significance of PhA° in the estimation of muscle strength: hand grip strength (HGS) and in that of respiratory muscles: maximal inspiratory pressure / max. expiratory pressure ratio (MIP/MEP). Furthermore, the relationship between PhA° and all-cause mortality in COPD patients was confirmed with the Cox regression model, Kaplan-Meier test, and log-rank tests. The role of malnutrition in idiopathic pulmonary fibrosis (IPF) is confirmed by the PhA° measurements which, regardless of body weight, is associated with the reduction in muscle mass of these patients, reduces their strength and exercise capacity, and greatly influences the prognosis. In conclusion PhA is a novel biomarker of morbidity and mortality in patients with severe respiratory diseases.

Chest wall reconstruction in benign and malignant tumors with non-rigid materials: An overview.

Several materials and techniques have been described for the procedure of chest wall reconstruction: the choice of using a technique or a material over another relies mainly on the surgeon's experience as well as thoracic defect localization and dimension, local availability of materials, and costs. From a technical point of view, autologous and alloplastic reconstruction are available, and, in both cases, rigid and non-rigid prostheses are found. Each material has its peculiarities, with advantages and disadvantages; thus, it is mandatory to be confident when planning the intervention to foresee possible complications and minimize them. We have reviewed the literature on chest wall reconstruction in chest wall tumors (both malignant and non malignant) with non-rigid prosthetic materials, focusing on safety outcomes.

Accuracy of a New Pulse Oximetry in Detection of Arterial Oxygen Saturation and Heart Rate Measurements: The SOMBRERO Study.

Early diagnosis and continuous monitoring of respiratory failure (RF) in the course of the most prevalent chronic cardio-vascular (CVD) and respiratory diseases (CRD) are a clinical, unresolved problem because wearable, non-invasive, and user-friendly medical devices, which could grant reliable measures of the oxygen saturation (SpO2) and heart rate (HR) in real-life during daily activities are still lacking. In this study, we investigated the agreement between a new medical wrist-worn device (BrOxy M) and a reference, medical pulseoximeter (Nellcor PM 1000N). Twelve healthy volunteers (aged 20−51 years, 84% males, 33% with black skin, obtaining, during the controlled hypoxia test, the simultaneous registration of 219 data pairs, homogeneously deployed in the levels of Sat.O2 97%, 92%, 87%, 82% [ISO 80601-2-61:2017 standard (paragraph EE.3)]) were included. The paired T test 0 and the Bland-Altman plot were performed to assess bias and accuracy. SpO2 and HR readings by the two devices resulted significantly correlated (r = 0.91 and 0.96, p < 0.001, respectively). Analyses excluded the presence of proportional bias. For SpO2, the mean bias was −0.18% and the accuracy (ARMS) was 2.7%. For HR the mean bias was 0.25 bpm and the ARMS3.7 bpm. The sensitivity to detect SpO2 ≤ 94% was 94.4%. The agreement between BrOxy M and the reference pulse oximeter was "substantial" (for SpO2 cut-off 94% and 90%, k = 0.79 and k = 0.80, respectively). We conclude that BrOxy M demonstrated accuracy, reliability and consistency in measuring SpO2 and HR, being fully comparable with a reference medical pulseoxymeter, with no adverse effects. As a wearable device, Broxy M can measure continually SpO2 and HR in everyday life, helping in detecting and following up CVD and CRD subjects.

Direct oral anticoagulant plasma levels in hospitalized COVID-19 patients treated with dexamethasone.

Direct oral anticoagulants (DOACs) are not recommended in COVID-19 patients receiving dexamethasone because of potential drug-drug and drug-disease interactions affecting anticoagulant concentration and activity. To evaluate short- and long-term pharmacokinetic interactions, serial through and peak DOAC plasma levels were prospectively measured during and after dexamethasone therapy, as well as during the acute phase and after recovery from COVID-19 in hospitalized, non-critically ill patients undergoing treatment with DOACs. Thirty-three (18 males, mean age 79 years) consecutive patients received DOACs (17 apixaban, 12 rivaroxaban, 4 edoxaban) for atrial fibrillation (n = 22), venous thromboembolism (n = 10), and acute myocardial infarction (n = 1). Twenty-six patients also received dexamethasone at a dose of 6 mg once daily for a median of 14 days. Trough DOAC levels on dexamethasone were within and below expected reference ranges respectively in 87.5 and 8.3% of patients, with no statistically significant differences at 48-72 h and 14-21 days after dexamethasone discontinuation. Peak DOAC levels on dexamethasone were within expected reference ranges in 58.3% of patients, and below ranges in 33.3%, of whom over two thirds had low values also off dexamethasone. No significant differences in DOAC levels were found during hospitalization and after resolution of COVID-19. Overall, 28 patients were discharged alive, and none experienced thrombotic or bleeding events. In this study, dexamethasone administration or acute COVID-19 seemed not to affect DOAC levels in hospitalized, non-critically ill COVID-19 patients.

Adherence, Persistence, and Effectiveness in Real Life. Multicenter Long-Term Study on the Use of Pirfenidone and Nintedanib in the Treatment of Idiopathic Pulmonary Fibrosis.

BACKGROUND: In the treatment of idiopathic pulmonary fibrosis (IPF), nintedanib and pirfenidone, with their different mechanisms of action, lead to a reduction in the rate of progression of the fibrosis process measured by the reduction of functional decline, and, in particular, the decrease in forced vital capacity (FVC) and of the diffusion capacity of the lungs for carbon monoxide (DLCO). The objective of this study was to analyze real-life adherence, persistence and efficacy in the use of pirfenidone and nintedanib in the treatment of IPF. METHODS: A non-interventional multicenter retrospective observational pharmacological study in real-life treat-ment at 1 and 2 years was conducted. Furthermore, we analyzed the levels of FVC and DLCO at 6 and 12 months, respectively, from the start of treatment. RESULTS: We identified 144 patients in the period between January 2013 and April 2019. From the point of view of adherence, there is no difference between the two drugs, even though patients who used pirfenidone had increasingly higher values: 0.90 vs 0.89, in the first year, and 0.91 vs 0.84, in the second year. In the first year of treatment, the percentage of persistent patients was 67% and 76%, while in the second year, it dropped to 47% and 53% for pirfenidone and nintedanib, respectively. CONCLUSION: The stratification of the adherence values as a function of the response to treatment in terms of FVC at 12 months for both study drugs showed that patients with optimal response scored adherence of more than 90%.

Radiomics-based machine learning differentiates "ground-glass" opacities due to COVID-19 from acute non-COVID-19 lung disease.

Ground-glass opacities (GGOs) are a non-specific high-resolution computed tomography (HRCT) finding tipically observed in early Coronavirus disesase 19 (COVID-19) pneumonia. However, GGOs are also seen in other acute lung diseases, thus making challenging the differential diagnosis. To this aim, we investigated the performance of a radiomics-based machine learning method to discriminate GGOs due to COVID-19 from those due to other acute lung diseases. Two sets of patients were included: a first set of 28 patients (COVID) diagnosed with COVID-19 infection confirmed by real-time polymerase chain reaction (RT-PCR) between March and April 2020 having (a) baseline HRCT at hospital admission and (b) predominant GGOs pattern on HRCT; a second set of 30 patients (nCOVID) showing (a) predominant GGOs pattern on HRCT performed between August 2019 and April 2020 and (b) availability of final diagnosis. Two readers independently segmented GGOs on HRCTs using a semi-automated approach, and radiomics features were extracted using a standard open source software (PyRadiomics). Partial least square (PLS) regression was used as the multivariate machine-learning algorithm. A leave-one-out nested cross-validation was implemented. PLS ß-weights of radiomics features, including the 5% features with the largest ß-weights in magnitude (top 5%), were obtained. The diagnostic performance of the radiomics model was assessed through receiver operating characteristic (ROC) analysis. The Youden's test assessed sensitivity and specificity of the classification. A null hypothesis probability threshold of 5% was chosen (p < 0.05). The predictive model delivered an AUC of 0.868 (Youden's index = 0.68, sensitivity = 93%, specificity 75%, p = 4.2 × 10-7). Of the seven features included in the top 5% features, five were texture-related. A radiomics-based machine learning signature showed the potential to accurately differentiate GGOs due to COVID-19 pneumonia from those due to other acute lung diseases. Most of the discriminant radiomics features were texture-related. This approach may assist clinician to adopt the appropriate management early, while improving the triage of patients.

Role of shear-wave and strain elastography to differentiate malignant vs benign subpleural lung lesions.

ABSTRACT: Elastosonography is a non-invasive diagnostic method to evaluate tissue stiffness. The aim of our study was to demonstrate the applicability and efficacy of elastosonography to differentiate benign vs malignant subpleural lung lesions compared to clinical, radiological and histological findings.We performed both strain and shear wave velocity (SWV) elastosonography on subpleural lung lesions. Moreover, we elaborated a composite score called "elasto index".Fourteen patients, 10 males and 4 females were recruited. On strain elastography, 9 lesions showed a hard pattern (type 3), 3 lesions showed an intermediate pattern (type 2), and 2 lesions a soft pattern (type 1). All lesions showed a mean SWV value of 4.46 ±â€Š2.37 m/second. The mean SWV for malignant lesions (n = 6) was 5.92 ±â€Š2.8 m/second. The mean SWV for benign lesions (n = 8) was 3.36 ±â€Š1.20 m/second. SWV shows an area under the curve (AUC) of 0.792, and the Youden index shows a value of 3.6 m/second. The ROC curve elaborated for the diagnosis of malignancy by strain elastography showed an AUC of 0.688. ROC curve for the diagnosis of malignancy by elasto index demonstrated an AUC of 0.802.SWV values obtained by ARFI elastosonographic method are higher in malignant lung lesions (mean SWV: 5.92 m/second) than in benign ones (mean SWV: 3.36); a composite score (elasto index) is characterized by better statistical significance for the differentiation of the lesions.

Smell and Taste in Severe CoViD-19: Self-Reported vs. Testing.

One of the most striking reported symptoms in CoViD-19 is loss of smell and taste. The frequency of these impairments and their specificity as a potential central nervous system function biomarker are of great interest as a diagnostic clue for CoViD-19 infection as opposed to other similar symptomatologic diseases and because of their implication in viral pathogenesis. Here severe CoViD-19 was investigated by comparing self-report vs. testing of smell and taste, thus the objective severity of olfactory impairment and their possible correlation with other symptoms. Because a significant discrepancy between smell and taste testing vs. self-report results (p < 0.001) emerges in our result, we performed a statistical analysis highlighting disagreement among normosmia (p < 0.05), hyposmia, severe hyposmia, and anosmia (p < 0.001) and, in hypogeusia and severe hypogeusia, while no differences are observed in normogeusia and ageusia. Therefore, we analyzed the olfactory threshold by an objective test revealing the distribution of hyposmic (34%), severe hyposmic (48%), and anosmic (13%) patients in severe CoViD-19. In severe CoViD-19 patients, taste is lost in 4.3% of normosmic individuals, 31.9% of hyposmic individuals, 46.8% of severe hyposmic individuals, and 17% of anosmic individuals. Moreover, 95% of 100 CoViD-19 patients objectively tested were affected by smell dysfunction, while 47% were affected by taste dysfunction. Furthermore, analysis by objective testing also highlighted that the severity of smell dysfunction in CoViD-19 subjects did not correlate with age and sex. In conclusion, we report by objective testing that the majority of CoViD-19 patients report severe anosmia, that most of the subjects have olfactory impairment rather than taste impairment, and, finally, that the olfactory impairment correlate with symptom onset and hospitalization (p < 0.05). Patients who exhibit severe olfactory impairment had been hospitalized for about a week from symptom onset; double time has taken place in subjects with normosmia. Our results may be limited by the relatively small number of study participants, but these suggest by objective testing that hyposmia, severe hyposmia, and anosmia may relate directly to infection severity and neurological damage. The smell test assessment could be a potential screening symptom that might contribute to the decision to test suspected cases or guide quarantine instructions, further therapeutic approach, and evaluation of neurological damage.

From an abdominal ultrasound to a lung disease passing through the diaphragm: a case of idiopathic pulmonary fibrosis.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by abnormal and excessive deposition of collagen in the pulmonary interstitium (fibrosis) with minimal associated inflammation evolving into progressive and irreversible decline in lung function. PATIENT CONCERNS: Patient referred discomfort, bilateral upper quadrant abdominal pain, and progressive exertional dyspnea (shortness of breath with exercise). DIAGNOSIS: Exertional dyspnea due to idiopathic pulmonary fibrosis (IPF). INTERVENTION: Sonographic evaluation demonstrated an alteration of diaphragm excursion together with a relevant alteration of the pleural line and multiple irregular and confluent B lines. CONCLUSIONS: Lung and diaphragm ultrasound could be employed as a screening or first-line diagnostic tool in the suspicion of interstitial lung disease.

Ultrasound evaluation of diaphragmatic mobility in patients with idiopathic lung fibrosis: a pilot study.

BACKGROUND: Some previous works have tested LUS use in diagnosing and monitoring interstitial lung diseases. B-lines are main sonographic signs for interstitial diseases. Increasing evidences suggest that dyspnea and impaired exercise capacity in IPF patients can be related, at least in part, to respiratory muscle dysfunction, in particular to diaphragm functionality. Both B-mode and M-mode ultrasound techniques have been employed to assess diaphragm excursion (DE), which measures the distance that the diaphragm is able to move during the respiratory cycle. METHODS: The main objective of this case-control study was to evaluate if differences exist between diaphragmatic excursions in IPF patients and in a control group of healthy subjects. Secondary objectives were to evaluate possible correlations among respiratory excursions, anthropometric parameters and respiratory function parameters. All patients performed spirometry and body plethysmography (PC). Diaphragm was examined by ultrasound imaging in B-MODE, and respiratory excursions were evaluated in M-MODE. Examination consisted of 3 measurements of the inspiratory phase at rest and after deep inspiration. RESULTS: Twelve patients with IPF and 12 healthy subjects were enrolled. There were no significant differences between respiratory excursions in patients and controls during spontaneous breathing, while there was a statistically significant difference between the mean values of the deep respiratory excursion in the two groups (p value < 0.001). There was a positive correlation between respiratory excursion with normal breath and chest circumference in controls (p = 0.034; R = 0.614) and in patients (p = 0.032; R = 0.37), but this relationship was not found even in subjects in deep breathing. A positive correlation was found between FVC values and diaphragmatic motility both at rest and in deep breathing in fibrotic patients. CONCLUSIONS: Diaphragmatic mobility is lower in IPF patients than in healthy controls, especially during deep inspiration. The correlation between reduced FVC and diaphragmatic excursion values in IPF patients can be of interest, since it could represent an index of functional respiratory function performed by a non-invasive, low-cost, simple and reliable imaging technique, such as LUS.

Supplementation with Qter® and Creatine improves functional performance in COPD patients on long term oxygen therapy.

BACKGROUND: Skeletal muscle dysfunction and poor functional capacity are important extra-pulmonary manifestations of chronic obstructive pulmonary disease (COPD), especially in COPD patients on long-term O2 therapy (LTOT). Beside the role of pulmonary rehabilitation, the effect of nutritional interventions is still controversial, and there are knowledge gaps on the effective role of nutraceutical supplementation on hard endpoints. The aim of this study was to investigate the effects of nutritional supplementation with Coenzyme Q10 (QTer®) - a powerful antioxidant with the potential to reduce oxidative stress and improve mitochondrial function - and Creatine on functional, nutritional, and metabolomic profile in COPD patients on long-term O2 therapy. METHODS: One-hundred and eight patients with COPD from 9 Italian hospitals were enrolled in this double-blinded randomized placebo-controlled clinical study. At baseline and after 2 months of therapy, the patients underwent spirometry, 6-minute walk test (6MWT), bioelectrical impedance analysis, and activities of daily living questionnaire (ADL). Also, dyspnea scores and BODE index were calculated. At both time points, plasma concentration of CoQ10 and metabolomic profiling were measured. FINDINGS: Ninety patients, who randomly received supplementation with QTer® and Creatine or placebo, completed the study. Compared with placebo, supplemented patients showed improvements in 6MWT (51 ±â€¯69 versus 15 ±â€¯91 m, p < 0.05), body cell mass and phase angle, sodium/potassium ratio, dyspnea indices and ADL score. The CoQ10 plasma concentration increased in the supplementation group whereas it did not change in the placebo group. The metabolomics profile also differed between groups. Adverse events were similar in both groups. INTERPRETATION: These results show that in patients with COPD, dietary supplementation with CoQ10 and Creatine improves functional performance, body composition and perception of dyspnea. A systemic increase in some anti-inflammatory metabolites supports a pathobiological mechanism as a reason for these benefits. Further trials should help clarifying the role of QTer® and Creatine supplementation in patients with COPD.

The earlier, the better: Impact of early diagnosis on clinical outcome in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a complex disease with a highly variable clinical course and generally poor prognosis. Classified as a rare disease, significant increases in incidence have been recorded worldwide in recent years. Left untreated IPF is extremely debilitating with substantial personal, social and economic implications. OBJECTIVES: To discuss how IPF is diagnosed and managed in real life clinical practice with particular reference to Italy and to determine how new and effective therapies can be incorporated into a patient-centred management approach in order to improve the lives of patients with IPF. OUTCOMES: Barriers to early diagnosis are discussed. Cited reasons for delays in diagnosing IPF in Italy include: inherent difficulties in diagnosis; lack of knowledge/awareness of the condition among point-of-contact healthcare professionals; delays in referral to centres of excellence and underestimation of symptoms by both patients and healthcare workers. Valid therapeutic options with demonstrated efficacy in slowing the decline in lung function are now available for patients with IPF. The ASCEND trial confirmed the effects of pirfenidone, approved for the treatment of IPF on the basis of the four phase III trials. Nintedanib, a tyrosine kinase inhibitor that targets the PDGF receptors α/ß, FGF receptors 1 to 3, and VEGF receptors 1-3, is approved in the USA and the EU for the treatment of IPF. The TOMORROW and the INPULSIS placebo controlled trials in patients with IPF confirm the efficacy and safety of nintedanib and recent interim analyses endorse its long-term effects in slowing disease progression. CONCLUSIONS: The importance of early and accurate diagnosis of IPF cannot be underestimated and it is the duty of all healthcare professionals to be vigilant to the symptoms of IPF and to involve a multidisciplinary team in diagnosing and managing IPF early in the course of disease.

Effects of nutraceutical diet integration, with coenzyme Q10 (Q-Ter multicomposite) and creatine, on dyspnea, exercise tolerance, and quality of life in COPD patients with chronic respiratory failure.

BACKGROUND: The protein-calorie malnutrition, resulting in muscle mass loss, frequently occurs in severe COPD patients with chronic respiratory failure (CRF), causing dyspnea, reduced exercise tolerance and impaired quality of life.The cause of this occurrence is an intake-output energy imbalance. A documented deficit of phosphocreatine and reduced mithocondrial energy production can contribute to this imbalance.Aim of this study is to verify whether a dietary supplementation with creatine and coenzyme Q10, important mitochondrial function factors, is able to influence this mechanism leading to a dyspnea reduction and improving exercise tolerance and quality of life. METHODS: 55 COPD patients with chronic respiratory failure (in long term O2 therapy), in stable phase of the disease and without severe comorbidities were assigned (double-blind, randomized) to: group A (30 patients) with daily dietary supplementation with Creatine 340 mg + 320 mg Coenzyme Q-Ter (Eufortyn®, Scharper Therapeutics Srl) for 2 months whereas Group B (25 patients) received placebo.All patients continued the same diet, rehabilitation and therapy during the study. At recruitment (T0) and after 2 months (T1), patients were submitted to medical history, anthropometry (BMI), bioelectrical impedance, arterial blood gas analysis, evaluation of dyspnea (VAS, Borg, BDI, MRC) and functional independence (ADL), 6-minute walk test (6MWT) and quality of life questionnaire (SGRQ). At 6 months and 1 year, a telephone follow up was conducted on exacerbations number. RESULTS: No significant difference was detected at baseline (T0) in the 2 groups. After 2 months of therapy (T1) the FFMI increased in the daily dietary supplementation group (+ 3.7 %) and decreased in the placebo group (- 0.6 %), resulting in a statistically significant (p < 0.001) treatment difference. Statistically significant treatment differences, favouring daily dietary supplementation group, were also seen for the 6MWT comparison. Group A patients also showed significant: 1) improvement in the degree of dyspnea (VAS: p < 0.05; Borg: p < 0.05; MRC: p < 0.001; BDI1: p < 0.05; BDI3: p < 0.03), and independence level in activities of daily living (p < 0.03); 2) improvement in quality of life in activity section (- 6.63 pt) and in total score (- 5.43 pt); 3) exacerbation number decrease (p < 0.02). No significant differences were found (end of study vs baseline) in group B. CONCLUSIONS: The nutraceutical diet integration with Q-Ter and creatine, in COPD patients with CRF in O2TLT induced an increasing lean body mass and exercise tolerance, reducing dyspnea, quality of life and exacerbations. These results provide a first demonstration that acting on protein synthesis and muscular efficiency can significantly modify the systemic consequences of the disease.

Systemic effects of COPD.

Chronic obstructive pulmonary disease (COPD) is characterised by a range of pathological changes of the respiratory system, including airflow limitation secondary to structural changes of the small airways and loss of alveolar attachments, inflammation, ciliary dysfunction, and increased mucous production. COPD also has significant systemic consequences. The relationships between these pulmonary and nonpulmonary morbidities are not fully understood, and this further complicates the assessment of disease severity and prognosis. Although improving lung function and disease symptoms have been the main focus of COPD management, these parameters alone do not reflect the full burden of disease. More recent endeavours have highlighted the potential role of addressing physical limitations imposed by systemic alterations. It is evident that systemic manifestations are common in COPD. Indeed, many patients demonstrate a gradual and significant weight loss that exacerbates the course and prognosis of disease. This weight loss is often accompanied by peripheral muscle dysfunction and weakness, which markedly contribute to exercise limitation and impaired quality of life. Weight loss has been postulated to be the result of a high metabolic rate that is not compensated for by increased dietary intake. The cause of this elevated metabolism is a matter of much debate, and several factors have been implicated. Similarly, the processes underlying depletion of muscle mass and function have not been fully delineated. The impact of the systemic manifestations of COPD is substantial, and although many attempts have been made to elucidate the mechanisms underlying these manifestations, there are important questions, which remain to be answered. An increase in our understanding in this field will doubtless highlight potential therapeutic targets, and assist in guiding future therapeutic development.