Endoscopic Management of Benign Airway Stenosis in Coronavirus Disease 2019 Patients.

BACKGROUND: The aims of this study were to evaluate the results of endoscopic dilation for simple benign airway stenosis in coronavirus disease 2019 (COVID-19) patients and whether COVID-19 infection was associated with higher rate of recurrence compared with a control group. METHODS: It was an observational multicenter study including consecutive patients with simple benign airway stenosis undergoing endoscopic dilatation with at least 6 months of follow-up. The outcome of patients with COVID-19 infection was compared with that of a control group in relation to patient and stenosis characteristics, and procedure type. Then, univariable and multivariable analyses identified the risk factors for recurrence. RESULTS: Seventy-nine patients were included in the study; 56 (71%) of these developed airway stenosis after COVID-19 infection. COVID-19 patients presented a higher rate of stenosis due to prolonged intubation (82 vs. 43%; p = 0.0014); no other differences were found regarding demographic data, characteristics of stenosis, and procedure type. Twenty-four (30%) patients had recurrence after first dilatation (32% for No-COVID-19 vs. 26% for COVID-19 group; p = 0.70), and in 11 (35%) of these, the stenosis recurred after repeated endoscopic treatment (65% for No-COVID-19 vs. 45% for COVID-19 group; p = 0.40). Subglottic stenosis (p = 0.013) and the use of laser (p = 0.016) were significant predictive factors for stenosis recurrence. CONCLUSION: COVID-19 infection did not affect the outcome of endoscopic treatment of simple airway stenosis, and the treatment of these subsets of patients should not differ from that of general population.

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.

Poor Nutritional Status and Dynapenia Are Highly Prevalent in Post-Acute COVID-19.

Poor nutritional status is common (estimated prevalence 5-69%) in acute coronavirus disease-2019 (COVID-19), and has been associated with hospitalization, the need for intensive care, and mortality. Body composition (BC) and muscle function have also been related in such patients to poor disease outcomes. As the evidence in the literature is limited, a cross-sectional study was carried out to determine the frequency of malnutrition in a cohort of post-acute COVID-19 patients referred to a rehabilitation center after hospital discharge. BC and muscle strength were assessed and the differences between bedridden and not bedridden patients were specifically evaluated. The study sample was composed of 144 post-acute COVID-19 patients (mean age 64.8 years; males = 95), 37% of whom were bedridden (males = 60%). Nutritional status was evaluated with Mini-Nutritional Assessment (MNA) and Controlling Nutritional status (CONUT). Fat-free mass (FFM) and skeletal muscle mass (SM) were estimated using bioelectrical impedance analysis (BIA). Raw BIA variables (phase angle = PhA and impedance ratios = IRs) were also determined and handgrip strength (HGS) was measured. Dynapenia was identified according to the 2019 EWGSOP criteria. According to MNA, 18% (n. 26) of patients were malnourished and 62% (n. 89) were at risk of malnutrition. As for CONUT, 21% (n. 31) of cases had moderate-severe malnutrition and 58% (n. 83) had light malnutrition. Abnormalities of raw BIA variables (low PhA and high IRs) and low HGS were more common in bedridden patients, in those who were malnourished, or had low FFM or SM. Dynapenic patients were 65% men and 47% women. In conclusion, malnutrition, BC alterations, and low HGS occur in post-acute COVID-19 patients and are more common in bedridden patients. Further studies are needed to identify reliable algorithms for assessing nutritional status in post-acute COVID-19 patients undergoing rehabilitation.

Genomic and Meiotic Changes Accompanying Polyploidization.

Hybridization and polyploidy have been considered as significant evolutionary forces in adaptation and speciation, especially among plants. Interspecific gene flow generates novel genetic variants adaptable to different environments, but it is also a gene introgression mechanism in crops to increase their agronomical yield. An estimate of 9% of interspecific hybridization has been reported although the frequency varies among taxa. Homoploid hybrid speciation is rare compared to allopolyploidy. Chromosome doubling after hybridization is the result of cellular defects produced mainly during meiosis. Unreduced gametes, which are formed at an average frequency of 2.52% across species, are the result of altered spindle organization or orientation, disturbed kinetochore functioning, abnormal cytokinesis, or loss of any meiotic division. Meiotic changes and their genetic basis, leading to the cytological diploidization of allopolyploids, are just beginning to be understood especially in wheat. However, the nature and mode of action of homoeologous recombination suppressor genes are poorly understood in other allopolyploids. The merger of two independent genomes causes a deep modification of their architecture, gene expression, and molecular interactions leading to the phenotype. We provide an overview of genomic changes and transcriptomic modifications that particularly occur at the early stages of allopolyploid formation.

Role of Rehabilitation Department for Adult Individuals With COVID-19: The Experience of the San Raffaele Hospital of Milan.

The rapid evolution of the health emergency linked to the spread of severe acute respiratory syndrome coronavirus 2 requires specifications for the rehabilitative management of patients with coronavirus disease 2019 (COVID-19). The symptomatic evolution of patients with COVID-19 is characterized by 2 phases: an acute phase in which respiratory symptoms prevail and a postacute phase in which patients can show symptoms related to prolonged immobilization, to previous and current respiratory dysfunctions, and to cognitive and emotional disorders. Thus, there is the need for specialized rehabilitative care for these patients. This communication reports the experience of the San Raffaele Hospital of Milan and recommends the setup of specialized clinical pathways for the rehabilitation of patients with COVID-19. In this hospital, between February 1 and March 2, 2020, about 50 patients were admitted every day with COVID-19 symptoms. In those days, about 400 acute care beds were created (intensive care/infectious diseases). In the following 30 days, from March 2 to mid-April, despite the presence of 60 daily arrivals to the emergency department, the organization of patient flow between different wards was modified, and several different units were created based on a more accurate integration of patients' needs. According to this new organization, patients were admitted first to acute care COVID-19 units and then to COVID-19 rehabilitation units, post-COVID-19 rehabilitation units, and/or quarantine/observation units. After hospital discharge, telemedicine was used to follow-up with patients at home. Such clinical pathways should each involve dedicated multidisciplinary teams composed of pulmonologists, physiatrists, neurologists, cardiologists, physiotherapists, neuropsychologists, occupational therapists, speech therapists, and nutritionists.

Antitussive therapy: A role for levodropropizine.

Cough is a protective reflex that serves to clear the airways of excessive secretions and foreign matter and which sometimes becomes excessive, and troublesome to patients. Cough is one of the most common reasons why individuals seek medical attention. A range of drugs have been developed in the past with antitussive activity and different mechanisms of action, but there are still very few safe and effective treatments available. The poor tolerability of most available antitussives is closely related to their action on the central nervous system (CNS). An international group of experts specialized in cough met to discuss the need to identify an effective antitussive treatment with a good tolerability profile. The aim of this expert review is to increase the knowledge about the cough mechanism and the activity of levodropropizine, a peripherally acting antitussive drug.

Early management of COPD: where are we now and where do we go from here? A Delphi consensus project.

PURPOSE: There is a lack of consensus on the most appropriate early diagnostic strategy, criteria for early access to treatment and follow-up approach for patients with COPD. MATERIALS AND METHODS: A Delphi consensus project investigated the early management of COPD. We formulated two questionnaires for completion by pneumologists in Italy. RESULTS: A total of 207 specialists completed questionnaire 1 and 184 of them questionnaire 2, between November 2016 and October 2017. Early diagnosis of COPD was considered uncommon for 93.2% of the expert panel. Regardless of the definition of "early diagnosis" - a diagnosis made before the clinical manifestation of the disease for most responders (60.4%) - experts were confident of the positive effects of early disease management, which they consider is effective in modifying the natural history of the disease. Lack of awareness of the disease was considered the first limiting factor to early COPD management for 78% of respondents. The most effective steps to reduce functional decline were considered to be smoking cessation, followed by long-acting ß2-agonist (LABA)/long-acting muscarinic antagonist (LAMA), LAMA, LABA, and finally inhaled corticosteroid/LABA (P<0.01 for each paired comparison). Specialists considered it "inappropriate" for general practitioners to perform both the early diagnosis and therapy of COPD without the involvement of a specialist. CONCLUSION: Early management of COPD is uncommon, and although data on the effects of early disease management on long-term outcomes are limited, Italian experts are confident of the clinical efficacy of this approach.

Raw Bioelectrical Impedance Analysis Variables Are Independent Predictors of Early All-Cause Mortality in Patients With COPD.

BACKGROUND: Bioelectrical impedance analysis (BIA) is a valuable method for estimating fat-free mass and fat mass in patients with COPD by using specific predictive equations. In addition, raw BIA variables such as high- to low-frequency impedance ratios (IRs) and phase angle, most likely as a result of providing information on muscle quality, have been related to disease severity and mortality in patients with several diseases but never in COPD. The aim of this study was to investigate the predictive role of raw BIA variables on 2-year survival in COPD. METHODS: Impedance (Z) at 5-10-50-100-250 kHz and phase angle at 50 kHz were determined in 210 patients with COPD. Three IRs were calculated: Z at 50 kHz/Z at 5 kHz (50/5 IR), Z at 100 kHz/Z at 5 kHz (100/5 IR), and Z at 250 kHz/Z at 5 kHz (250/5 IR). Demographic, respiratory, and body composition data at baseline were recorded. All-cause mortality was assessed during 2 years of follow-up. RESULTS: After the follow-up period, all-cause mortality was 13.8%. Statistically significant differences between nonsurvivors and survivors emerged in terms of age, weight, BMI, FEV1, inspiratory capacity, and modified Medical Research Council dyspnea score. With respect to nutritional variables, nonsurvivors had lower fat-free mass (P = .031), lower fat mass (P = .015), higher IRs (P < .001 for all the ratios), and lower phase angle (P < .001) compared with survivors. After adjustment for confounding factors, each unit increase of IRs and each unit decrease of phase angle were associated with a higher risk of death. CONCLUSIONS: IRs and phase angle, as raw BIA variables, are independent and powerful predictors of all-cause mortality in COPD and should be considered, together with inspiratory capacity and 6-min walk distance, as significant prognostic factors in the short- to middle-term.

Omalizumab, the first available antibody for biological treatment of severe asthma: more than a decade of real-life effectiveness.

Omalizumab was the first, and for a long time the only available monoclonal antibody for the add-on treatment of severe allergic asthma. In particular, omalizumab selectively targets human immunoglobulin (Ig)E, forming small-size immune complexes that inhibit IgE binding to its high- and low-affinity receptors. Therefore, omalizumab effectively blunts the immune response in atopic asthmatic patients, thus significantly improving the control of asthma symptoms and successfully preventing disease exacerbations. These very positive effects of omalizumab make it possible to drastically decrease both referrals to the emergency room and hospitalizations for asthma exacerbations. Such important therapeutic actions of omalizumab have been documented by several randomized clinical trials, and especially by more than 10 years of real-life experience in daily clinical practice. Omalizumab can also interfere with airway remodelling by inhibiting the activation of IgE receptors located on structural cells such as bronchial epithelial cells and airway smooth muscle cells. Moreover, omalizumab is characterized by a very good safety and tolerability profile. Hence, omalizumab represents a valuable therapeutic option for the add-on biological treatment of severe allergic asthma.

Malnutrition and sarcopenia assessment in patients with chronic obstructive pulmonary disease according to international diagnostic criteria, and evaluation of raw BIA variables.

BACKGROUND: Various criteria have been used so far for the diagnosis of malnutrition or sarcopenia in patients suffering from chronic obstructive pulmonary disease (COPD). OBJECTIVE: To determine the prevalence of malnutrition and sarcopenia in COPD, as defined by international diagnostic criteria, and determine their relationships with raw BIA variables. METHODS: Two-hundred and sixty-three COPD patients (185 males and 78 females) underwent both clinical examination and respiratory, anthropometric, bioelectrical impedance analysis (BIA raw variables: phase angle and impedance ratio), handgrip strength (HGS), 4 m gait speed and biochemical measurements. Malnutrition and sarcopenia were diagnosed based on European Society for Clinical Nutrition and Metabolism (ESPEN) criteria and European Working Group on Sarcopenia in Older People (EWGSOP) criteria, respectively. RESULTS: The overall prevalence of malnutrition and sarcopenia was 19.8% and 24.0% respectively, increasing with disease severity. The prevalence of sarcopenia was significantly higher in patients with malnutrition (71.2% vs 12.3%; p < 0.001), especially in those with systemic inflammation (cachectic patients) (85.7% vs 61.3%; p < 0.001). Malnourished patients with sarcopenia had a significant reduction in BMI, fat-free mass and HGS compared to non-sarcopenic patients. Finally, impedance ratio significantly increased and phase angle decreased in patients with severe sarcopenia and in cachectic patients. CONCLUSION: A relatively high prevalence of malnutrition and sarcopenia was found in COPD patients applying international standard criteria, with some discrepancy between the two diagnoses. In addition, clear-cut changes in raw BIA variables were observed in malnourished patients with systemic inflammation and sarcopenic patients.

Evaluation of body composition in COPD patients using multifrequency bioelectrical impedance analysis.

BACKGROUND: Multifrequency bioelectrical impedance analysis (MF-BIA) is a technique that measures body impedance (Z) at different frequencies (5, 10, 50, 100, and 250 kHz). Body composition may be estimated using empirical equations, which include BIA variables or, alternatively, raw BIA data may provide direct information on water distribution and muscle quality. OBJECTIVES: To compare raw MF-BIA data between COPD patients and controls and to study their relationship with respiratory and functional parameters in COPD patients. METHODS: MF-BIA was performed (Human Im-Touch analyzer) in 212 COPD patients and 115 age- and BMI-matched controls. Fat-free mass (FFM) and fat mass were estimated from BIA data, and low- to high-frequency (5 kHz/250 kHz) impedance ratio was calculated. Physical fitness, lung function and respiratory muscle strength were also assessed in COPD patients. RESULTS: After adjusting for age, weight, and body mass index, FFM and the 5/250 impedance ratio were lower in COPD patients (P<0.001) and were negatively affected by disease severity. In both male and female patients, the 5/250 impedance ratio was significantly correlated mainly with age (r=-0.316 and r=-0.346, respectively). Patients with a 5/250 impedance ratio below median value had lower handgrip strength (P<0.001), 6-minute walk distance (P<0.005), respiratory muscle strength (P<0.005), forced expiratory volume in 1 second (P<0.05) and vital capacity (P<0.005). Finally, the 5/250 impedance ratio was reduced (P<0.05) in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) III and IV (compared to those with GOLD I and II) or a BODE index between 6 and 10 points (compared to those with BODE index between 1 and 5 points). CONCLUSION: MF-BIA may be a useful tool for assessing body composition and nutritional status in COPD patients. In particular, the impedance ratio could give valuable information on cellular integrity and muscle quality.

Preliminary study on the assessment of visceral adipose tissue using dual-energy x-ray absorptiometry in chronic obstructive pulmonary disease.

BACKGROUND: Visceral adipose tissue (VAT) was shown to be increased in patients with chronic obstructive pulmonary disease (COPD) compared to control subjects with comparable body mass index (BMI). Our aim was to determine the relation of VAT by dual-energy x-ray absorptiometry (DEXA) in patients with COPD by disease severity, BMI, other indices of body composition and static lung volumes. METHODS: 294 COPD patients admitted for rehabilitation were studied. Lung function, static lung volumes and body composition (i.e. BMI, waist circumference, fat-free mass, fat mass and fat distribution between android and gynoid fat mass) were assessed before entering pulmonary rehabilitation. VAT was estimated within the android region by using DEXA. Patients were stratified for gender, BMI (cut-off of 25 kg/m2) and GOLD stage. To assess the impact of VAT on lung volumes, patients were also stratified for VAT less and above 50th percentile. RESULTS: Both male and female patients with more severe airflow limitation had significantly lower VAT values, but these differences disappeared after stratification for BMI. VAT was significantly and strongly correlated with other body composition parameters (all p < 0.001). Patients with moderate to severe airflow limitation and lower VAT had increased static lung hyperinflation and lower diffusing capacity for carbon monoxide. Nevertheless, multivariate stepwise regression models including for BMI, age, gender and forced expiratory volume in 1 s (FEV1) as confounders did not confirm an independent role for VAT on static lung hyperinflation and diffusion capacity. CONCLUSION: After stratification for BMI, VAT is comparable in moderate to very severe COPD patients. Furthermore, BMI and demographics, but not VAT, were independent predictors of static lung hyperinflation and diffusing capacity in COPD.

Prospective study of the efficacy of antibiotics versus antitussive drugs for the management of URTI-related acute cough in children.

BACKGROUND: Acute cough is one of the most frequent symptoms prompting a visit to a health care provider, usually following a viral upper respiratory tract infection (URTI). The disproportionate use of antibiotics in children with URTIs, recently highlighted in the medical literature, could lead to associated side effects, without any beneficial effect. Although an early, albeit inappropriate, antibiotic prescription increases parental satisfaction, URTIs are predominantly viral infections and are generally self-limiting. Therefore the aim of this study was to analyze the effectiveness of antibiotics compared to symptomatic drugs (central and peripheral antitussives) on URTI-related cough in a pediatric population. METHODS: This is a prospective observational study of 330 children who required pediatric consultation for acute cough. Severity, frequency and type of cough were assessed at baseline and after 6 days of treatment (antitussives n = 123, antibiotics n = 89 or combination of them n = 38) or no treatment (n = 80). The outcome of cough management after 6 days was analyzed in terms of resolution, improvement, no change or worsening of symptoms. Study assessments were performed using a standardized questionnaire administered to parents. RESULTS: Between children treated with antitussives or antibiotics, there was a statistically significant difference in the resolution of cough. Moreover, if considering peripheral antitussives, the resolution of cough was significantly higher with antitussives than with antibiotics (p < 0.01). There was no difference in cough resolution between children treated with antitussives and those receiving a combination of antibiotics and antitussives, either central and peripheral antitussives. CONCLUSION: Antibiotics are generally not useful nor appropriate in treating acute cough due to the common cold. Furthermore, inappropriate antibiotic use introduces the possibility of adverse side effects as well as promotion of antibiotic resistance. The findings of the present study suggest that antitussives, especially peripherally acting agents, represent an effective treatment option for acute pediatric cough caused by URTIs.

WITHDRAWN: Treatment Effect of Combination of Nsaid and Antitussives in Patients With URTI-Related Cough.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Eur Respir J. 46 (2015) PA3852, http://dx.doi.org/10.1183/13993003.congress-2015.PA3852. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

WITHDRAWN: Combination of NSAID and Antitussives in Treatment of URTI Related Cough: An Observational Study.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Eur Respir J. 46 (2015) PA3852, http://dx.doi.org/10.1183/13993003.congress-2015.PA3852. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Levodropropizine for treating cough in adult and children: a meta-analysis of published studies.

BACKGROUND: Cough is one of the most common symptoms for which patients seek medical attention from primary care physicians and lung specialists. About 40% of the population at any one time report cough. Cough is associated with significantly impaired health-related quality of life. Levodropropizine is an effective and very well tolerated peripheral antitussive drug. We want to compare it to central cough suppressants efficacy (opioids and non-opioids) that may be associated with side effects limiting their use. METHODS: After a comprehensive literature search, a meta-analysis of 7 clinical studies of levodropropizine vs. control, including a total of 1,178 patients, was performed with the aim to evaluate the overall comparative efficacy of levodropropizine in the pediatric and adult population. Three electronic databases and reference list were used to search for studies that assessed the efficacy of levodropropizine for treating cough in children and adults using as standardized efficacy parameters the cough frequency and severity, and number of night awakenings as outcome parameters. RESULTS: The meta-analysis of all standardized efficacy parameters showed a highly statistically significant difference in the overall antitussive efficacy in favor of levodropropizine vs. control treatments (p = 0.0015). The heterogeneity test for the efficacy outcome was not statistically significant (p = 0.0534). Seven studies met out inclusion criteria. A meta-analysis of the eligible ones showed a statistically significant difference in the overall anti-tussive effect of levodropropizine versus control (p = 0.0015). CONCLUSIONS: This analysis indicates that levodropropizine is an effective antitussive drug in children and adults, with statistically significant better overall efficacy outcomes vs. central antitussive drugs (codeine, cloperastine, dextromethorphan) in terms of reducing cough intensity and frequency, and nocturnal awakenings. This result further reinforces the favorable benefit/risk profile of levodropropizine in the management of cough. The efficacy of levodropropizine in the treatment of cough in children and adults is higher than that of the common centrally-acting anti-tussive.

A prospective multicentric study of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease and different clinical phenotypes.

BACKGROUND: Recently, it has been proposed that different clinical phenotypes can be recognized in patients with chronic obstructive disease (COPD), namely predominant airway disease or parenchymal destructive changes. OBJECTIVES: The aim of this prospective multicenter study was to evaluate whether these two phenotypes may influence outcomes following a pulmonary rehabilitation program (PRP). METHODS: We have prospectively evaluated 364 consecutive COPD patients (70 ± 8 years, 76.3% males) admitted to a standard hospital-based PRP in 6 Italian centers. According to their phenotype, the study cohort was divided into two groups: patients with airway obstructive (group 1, n = 208) or parenchymal destructive COPD (group 2, n = 156). Before and after PRP, values of 6-min walking distance, perceived breathlessness (Medical Research Council), health-related quality of life (St. George's Respiratory Questionnaire) and respiratory muscle function (maximal inspiratory and expiratory pressure) were recorded. RESULTS: PRP resulted in significant improvements in all outcome measures without any significant differences between groups. CONCLUSIONS: Our study confirms that COPD patients may benefit from pulmonary rehabilitation independent of their clinical phenotype.

Anatomy and neuro-pathophysiology of the cough reflex arc.

Coughing is an important defensive reflex that occurs through the stimulation of a complex reflex arc. It accounts for a significant number of consultations both at the level of general practitioner and of respiratory specialists. In this review we first analyze the cough reflex under normal conditions; then we analyze the anatomy and the neuro-pathophysiology of the cough reflex arc. The aim of this review is to provide the anatomic and pathophysiologic elements of evaluation of the complex and multiple etiologies of cough.